Feeds:
Posts
Comments

Posts Tagged ‘European Patent Convention’


Endothelial Dysfunction, Diminished Availability of cEPCs,  Increasing  CVD Risk — Macrovascular Disease – Therapeutic Potential of cEPCs

Author and Investigator Initiated Study: Aviva Lev-Ari, PhD, RN

In normal conditions, the vascular endothelium produces and secretes substances that modulate vascular tone and protect the vessel wall from inflammatory cell infiltration, thrombus formation, and vascular smooth muscle cell proliferation (Rubanyi, 1993). Pathologic conditions such as hyperlipidemia, hyperglycemia, and hypertension impair the ability of the vascular endothelium to produce vasodilatory and anti-adhesion moieties and increase the production of vasoconstrictor, proadhesion, and pro-thrombotic molecules, leading to elevated vascular tone, enhanced cell adhesion, proliferation of media smooth muscle cells, and propensity toward thrombosis (Drexler & Hornig, 1999),(Endemann & Schiffrin, 2004). Endothelial cell loss and turnover are accelerated in the presence of hemodynamic and biochemical alterations and are a prominent feature of vascular injury resulting from percutaneous coronary intervention (Bennett & O’Sullivan, 2001).

The loss of endothelial function and integrity sets in motion the cascade of events that lead to atherosclerosis and restenosis after percutaneous revascularization (Ross, 1999),(Dzau et al., 2002). Processes of mobilization, growth, differentiation, recruitment, homing, replication and migration characterize cEPCs from the initial cell division of stem cells to cell apoptosis. What are the factors influencing cEPC mobilization, growth, differentiation, recruitment, mobilization, homing, replication and migration?

Physiological Factors

Chemokines

SCF-1, G-CSF, GM-CSF

Effect on cEPCs: recruitment, mobilization (Takahashi et al., 1999), (Kong et al., 2004a), (Kocher et al. 2001), (Shi et al., 1998), (Cho et al., 2003),(Orlic et al., 2001),(Bhattacharya et al., 2000), (Shi et al, 2002)

SDF-1

Effect on cEPCs: recruitment, mobilization, homing (Yamaguchi et al., 2003),(Powell et al., 2005),(Askari et al., 2003), (Hiasa et al., 2004),(George et al., 2003),(George et al., 2004),(Massa et al., 2005)

Cytokines / Growth Factors

FGF, VEGF, PIGF

Effect on cEPCs: mobilization, differentiation (Kalka et al., 2000a),(Ashara et al., 1997),(Kalka et al., 2000b)

                                  Angiopoietin, PDGF

Effect on cEPCs: differentiation

Hormones

Erythropoietin

Effect on cEPCs: mobilization, replication (Heeschen et al., 2003), (George, et. al., 2005).

Estrogen

Effect on cEPCs: mobilization (Strehlow et al., 2003), (Imanishi et al., 2005)

Signaling molecules

NO, Akt

Effect on cEPCs: mobilization, differentiation(Aicher et al., 2003).

 

Pharmacological Factors

3-HMC-CoA Inhibitors (statins)

Effect on cEPCs: mobilization, migration, homing (Werner et al., 2003),(Vasa et al., 2001a),(Walter et al., 2002),(Dimmeler et al., 2001),

(Llevadot et al., 2001),(Spyridopoulos et al., 2004)

             PPAR-gamma Agonists

Effect on cEPCs: mobilization, differentiation (Verma & Szmitko, 2006), (Andrew et al., 2004)

Physical Factors

 

            Exercise, hypoxia

Effect on cEPCs: mobilization (Laufs et al., 2003),(Kleinman et al., 2005),(Goon et al., 2006)

Pathological Factors

Coronary artery disease (CAD)

Effect on cEPCs: mobilization, homing (Kalka et al., 2000a),(Vasa et al., 2001b),(Heeschen et al., 2004)

Acute MI

Effect on cEPCs: mobilization, homing (Shintani et al., 2001),(Valgimigli et al., 2004),(Massa et al., 2005)

Peripheral limb ischemia

Effect on cEPCs: mobilization, homing (Takahashi et al., 1999),(Iwaguro et al., 2002),(Asahara et al., 1997),(Kalka et al., 2000b)

Vascular injury and inflammation

Effect on cEPCs: mobilization, homing (Ross, 1999),( Losordo et al., 2003), (Dimmeler & Zeiher, 2004),(Werner et al., 2003),(Verna et al, 2004).

EPC transplantation has been shown to induce new vessel formation in ischemic myocardium and hind limb (Kalka et al., 2000c),(Kawamoto et al, 2001),(Kocher, 2001) and to accelerate re-endothelialization of injured vessels and prosthetic vascular grafts in humans and in various animal models (Kocher, 2001),(Griese et al., 2003) demonstrating their therapeutic potential as a cell-based strategy for rescue and repair of ischemic tissues and injured blood vessels. Furthermore, EPCs are amenable to genetic manipulation, underscoring their usefulness as vectors for local delivery of therapeutic genes (Griese et al., 2003),(Kong et al., 2004b), (Iwaguro, 2002)

   Clinical Frontiers and Therapeutic Applications of cEPCs

  • Angiogenesis
  • Neovascularization of Artherosclerotic Plaque
  • Risk Factors impairing Collateral Development
  • Inhibitory Effects of Hypercholesterolemia
  • Bone Marrow Cells: Supporting cells in vascular growth processes
  • Inverse Relations: cEPCs and Risk of Macrovascular Events
  • New Stenting Technology:

 

  1.    Stents eluting Nitric Oxide (Verma and Marsden, 2005)
  2.    Stents coated with antiboby specific (anti-CD34) to the EPCs antigen cell     (Chadwick, 2006),(Aoki et al., 2005)
  3.    EPC-covered intravascular stents deployed for prevention of stent  thrombosis and restenosis as well as for rapid  formation of normal tissue architecture (Shirota et al., 2003).

 

  1. Table 1:            Alterations in number and function of cEPCs Disease Characterization and Suitability for ElectEagle an Endogenous Augmentation Method for cEPCs number (not for cEPCs function)

Disease Type

(Dzau et al., 2005)

Number

of

 cEPCs

Function

of

cEPCs

References

Disease Suitability for Endogenous Augmentation of cEPCs
Myocardial
     CAD

down

 down

(Kalka et al., 2000a),(Shintani et al., 2001),(Vasa et al., 2000b),(Hill et al., 2003),(Heeschen et al., 2004)

yes

     CHF

down

down

(Valgimigli et al.,2004),(Massa et al., 2005)

yes

     Unstable angina

down

unknown

(George et al., 2004)

yes

     MI

up

down

(Massa et al., 2005)

No

Vascular
     Atherosclerosis

down

down

(Vasa et al., 2001b),(Heeschen, 2004)(Lusis, 2000)

yes

     Acute Vascular injury and inflammation

up

unknown

(Fuujiyama et al.,2003)(Werner et al., 2003),(Walter et al., 2002),(Strehlow et al., 2003),(Shi et al., 1998),(Gill et al., 2001),

(Chu et al., 2003)

No

     PeripheralLimb ischemia

up

unknown

(Takahashi et al.,1999),(Iwaguro et al., 2002),(Asahara et al., 1997),(Asahara et al., 1999),(Kalka et al., 2000b)(Segal at al., 2006)

No

     Transplantarteriopathy

down

unknown

(Simper at al., 2003)

Yes

     In-stentrestenosis

down

unknown

(George et al., 2003)

yes

     Hypertension

unknown

unknown

No

     Hyperlipidemia

down

down

(Rauscher et al., 2003)

yes

Diabetes

down

down

(Loomans et al.,2004),(Tepper et al., 2002)

yes

Renal Failure
     Hemodialysis

down

down

(Choi et al., 2004)

yes

Source: original table created by Lev-Ari, A.

Based on Table 1, above, Lev-Ari, A. concluded that four Cardiovascualr diseases are NOT candidates for cEPCs therapeutic treatment

List of Disease unsuitable for ElectEagle an Endogenous Augmentation Method for  cEPCs includes:

  • Myocardial infarction
  • Acute Vascular injury and inflammation
  • Peripheral Limb ischemia
  • Hypertension

Table 2:           Therapeutic Angiogenesis Effects achieved by Cell-Based Therapy: Donor, Human; Recipient, Autologous;

Diagnosis, Myocardial Infarction

 

Therapeutic

Effect

Measured

Effect

Method of Delivery

Type and

Source of Cells

References

EjectionFruction

Up

(Stamm et al.,2003)

(Assmus et al., 2002),

(Britten et al., 2003),

(Schachinger et al., 2004),

(Wollert et al., 2004)

(Fernandez-Aviles

et al., 2004),

(Kang et al., 2004)

 

Infarct border

(Stamm et al., 2003)

CD133

(Stamm et al., 2003),

 

BM

(Stamm et al., 2003)

(Stamm et al., 2003)

Collateral flow (SPECT)

Up

(Stamm et al., 2003)

Infarct size

Down

(Strauer et al., 2002)

Intracoronary Balloon

Catheter

(Strauer et al., 2002)

BM

(Strauer et al., 2002)

(Strauer et al., 2002)

Wall motion

Up

(Strauer et al., 2002)

Contractility

Up

(Assmus et al., 2002),

(Britten et al., 2003),

(Schachinger et al., 2004),

(Wollert et al., 2004)

Intracoronary Balloon

Catheter

(Assmus et al., 2002),

(Britten et al., 2003),

(Schachinger et al., 2004),

(Wollert et al., 2004)

BM

PB

MNC

(Assmus et al., 2002),

(Britten et al., 2003),

(Schachinger et al., 2004),

(Wollert et al., 2004)

(Assmus et al., 2002),(Britten et al., 2003),(Schachinger et al., 2004),

(Wollert et al., 2004)

Myocardial perfusion

Up

(Assmus et al., 2002),

(Britten et al., 2003),

(Schachinger et al., 2004),

(Wollert et al., 2004)

Remodeling

Down

(Assmus et al., 2002),

(Britten et al., 2003),

(Schachinger et al., 2004),

(Wollert et al., 2004)

LV wall thickness

Up

(Fernandez-Aviles et al., 2004)

Intracoronary w/PCA

(Fernandez-Aviles et al., 2004)

CD34+

CD117+

AC133+

(Fernandez-Aviles et al., 2004)

End-systolic (ESV) volume

Down

(Fernandez-Aviles et al., 2004)

Exercise time

Up

(Kang et al., 2004)

Intracoronary

G-CSF

CD34+

(Kang et al., 2004)

 

Table 3:          

Therapeutic Angiogenesis Effects achieved by Cell-Based Therapy: Donor, Human; Recipient, Autologous;

Diagnosis, Myocardial Ischemia – Unstable Ischemia

 

Therapeutic

Effect

Measured

Effect

Method of Delivery

Type and

Source of Cells

References

Ejection Fruction

Up

(Perin et al., 2003),

(Tse et al., 2003)

Transendocardial with NOGA mapping

MNCs

(Perin et al., 2003),

(Tse et al., 2003)

BM

(Perin et al., 2003),

(Tse et al., 2003)

(Perin et al., 2003),

(Tse et al., 2003)

Anginal episodes

Down

(Perin et al., 2003),

(Tse et al., 2003)

Wall thickening

Up

(Perin et al., 2003),

(Tse et al., 2003)

Wall motion

Up

(Perin et al., 2003),

(Tse et al., 2003)

REFERENCES

Aicher A, Heeschen C, Mildner-Rihm C, Urbich C, Ihling C, Technau- Ihling K, Zeiher AM, Dimmeler S, (2003). Essential role of endothelial nitric oxide synthase for mobilization of stem cell and progenitor cells. Nat Med., 9:1370-1376.

Anderson T. (1999). Assessment of treatment of endothelial dysfunction. J Am Coll of Cardiology, 34: 631- 8.

Andrew C. Li, Binder, CJ, Gutierrez, A, Brown, KK, Plotkin, CR, Pattison, JW, Valledor, AF, Davis, RA, Willson, TM, Witztum, JL, Palinski, W, Glass, CK. (2004). Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPAR-alpha, Beta/delta, and gamma. J. Clin. Invest. 114:1564-1576

http://www.jci.org/articles/view/18730

Aoki, J., Serruys, P.W., van Beusekom, H., Ong, A.T., McFadden, E.P., Sianos, G., et al. (2005). Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry. J Am Coll Cardiol 45 (10), 1574–1579.

Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatterman G, and Isner JM (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science 275: 964–967.

Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM. (1999). Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res. 85:221–228.

Askari AT, Unzek S, Popovic ZB, Goldman CK, Forudi F, Kiedrowski M, Rovner A, Ellis SG, Thomas JD, DiCorleto PE, Topol EJ, Penn MS.(2003). Effect of stromal cell-derived factor 1 on stem cell homing and tissue regeneration in ischemic cardiomyopathy. Lancet, 362:697–703.

Assmus B, Schachlinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM, (2002). Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation, 106:3009 –3017

Bennett MR, O’Sullivan MO (2001). Mechanisms of angioplasty and stent restenosis: implications for design of rational therapy. Pharmacol Ther., 91:149 –166.

Ben-Shoshan, J and George, J. (2006). Endothelial progenitor cells as therapeutic vectors in cardiovascular disorders: from experimental models to human trials  Pharmacology Therapeutics (impact factor: 8.9). 08/2007; 115(1):25-36.

Bhattacharya V, Shi Q, Ishida A, Sauvage LR, Hammond WP, Wu MH.(2000). Administration of granulocyte colony-stimulating factor enhances endothelialization and microvessel formation in small caliber synthetic vascular grafts. J Vasc Surg., 32:116 –123.

Bonetti PO, et al. (2002). Reactive hyperemia peripheral arterial tonometry, a novel non-invasive index of peripheral vascular function, is attenuated in patients with coronary endothelial dysfunction. Circulation, 106:Suppl II:579.

Bonetti PO, et al. (2003). Enhanced external counterpulsation improves endothelial function in patients with symptomatic coronary artery disease. J Am Coll of Cardiology, 41:1761-8.

Britten MB, Abolmaali ND, Assmus B, Lehman R, Honold J, Schmitt J, Vogl TJ, Martin H, Schachinger V, Dimmeler S, Zeiher AM, (2003). Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation, 108:2212–2218.

Bypass Angioplasty Revascularization Investigation in Type 2 Diabetics (BARI 2D) ClinicalTrials.gov Identifier: NCT00006305, 2000-2007

http://www.nejm.org/doi/full/10.1056/NEJMoa0805796

Caplice NM, Bunch TJ, Stalboerger PG, Wang S, Simper D, Miller DV, Russell SJ, Litzow MR, Edwards WD. (2003). Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation. Proc Natl Acad Sci U S A. 100: 4754–4759.

Chadwick , D.(2006) OrbusNeich’s Genous Bioengineered R-stent . Cath Lab Digest, 14 (1), 20-26

Cho H-J, Kim H-S, Lee M-M, Kim D-H, Yang H-J, Hur J, Hwang K-K, Oh S, Choi Y-J, Chae I-H, Oh, B-H, Choi Y-S, Walsh K, Park Y-B. (2003).  Mobilized endothelial progenitor cells by granulocyte-macrophage colony-stimulating factor accelerate reendothelialization and reduce vascular inflammation after intravascular radiation. Circulation, 108:2918 –2925.

Choi J-H, Kim KL, Huh W, Kim B, Byun J, Suh W, Sung J, Jeon E-S, Oh H-Y, Kim D-K, (2004). Decreased number and impaired angiogenic function of endothelial progenitors in patients with chronic renal failure. Arterioscler Thromb Vasc Biol.,24:1246 –1252.

Cinamon G, Shinder V, Alon R (2001) Shear forces promote lymphocyte migration across vascular endothelium bearing apical chemokines. Nature Immunology, 2:515

Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, Rutten H, Fichtlscherer S, Martin H, Zeiher AM, (2001). HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI3-kinase/Akt pathway. J Clin Invest., 108:391–397.

Dimmeler S and Zeiher AM, (2004). Vascular repair by circulating endothelial progenitor cells: the missing link in atherosclerosis. J Mol Med. 82:671– 677.

Drexler H and Hornig B, (1999). Endothelial dysfunction in human disease. J Mol Cell Cardiol., 31:51– 60.

Dzau VJ, Braun-Dullaeus RC, Sedding DG. (2002). Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies. Nat Med.,  8:1249 –1256.

Dzau, VJ, Gnecchi, M, Pachori, AS, Morello F, Melo, LG.(2005).Therapeutic Potential of Endothelial Progenitor Cells in Cardiovascular Diseases.Hypertension,246:7-18.

Edelberg JM, Tang L, Hattori K, Lyden D, Rafii. (2002). Young adult bone marrow-derived endothelial precursor cells restore aging-impaired cardiac angiogenic function. Circ Res., 90:e89–e93.

Endemann DH and Schiffrin EL, (2004). Endothelial dysfunction. J Am Soc Nephrol., 15:1983–1992.

Fadini, G, Avogaro A, Agostini C. (2004), Unambiguous Definition of Endothelial Progenitor Cells. Electronic Letter to the Editor of Heart in reference to article by Eizawa, T, Ikeda U, et al. Decreasing in circulating endothelial progenitor cells in patients with stable CAD, Heart, 2004; 90: 685-686,

http://heart.bmjjournals.com/cgi/eletters/90/6/685#310  retrieved on 6/26/2006Link not found 5/1/2013

Fernandez-Aviles F, San Roman JA, Garcıa-Frade J, Fernandez ME, Penarrubia MJ, de la Fuente Luis, Gomez-Bueno M, Cantalapiedra A, Fernandez J, Gutierrez O, Sanchez PL, Hernandez C, Sanz R, Garcıa- Sancho J, Sa´nchez A, (2004). Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res., 95:742–748.

Folsom, A.R. Chambless, L.E. Ballantyne, C.M. Coresh, J. Heiss, G. Wu, K.K. Boerwinkle, E. Mosley, T.H. Sorlie, P. Diao, G. Sharrett, A.R. (2006). An Assessment of Incremental Coronary Risk Prediction Using C-Reactive Protein and Other Novel Risk Markers – The Atherosclerosis Risk in Communities Study. Arch Intern. Med. 166, 1368-1373.

Fuujiyama S, Amano K, Uehira K, Yoshida N, Nishiwaki Y, Nozawa Y,  Jin D, Takai S, Miyazaki M, Egashira K, Imada T, Iwasaka T, Matsubara H, (2003). Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells. Circ Res., 93:980-989.

George F, Brisson C, Poncelet P, Laurent JC, Massot O, Arnoux D, Ambrosi P, Klein-Soyer C, Cazenave JP, and Sampol J (1992). Rapid isolation of human endothelial cells from whole blood using S-Endo 1 monoclonal antibody coupled to immunomagnetic beads: demonstration of endothelial injury after angioplasty.Thromb Haemost, 67:147–153.

George J, Herz I, Goldstein E, Abashidze S, Deutch V, Finkelstein A, Michowitz Y, Miller H, Keren G.(2003). Number and adhesive properties of circulating endothelial progenitor cells in patients with in-stent restenosis. Arterioscler Thromb Vasc Biol., 23:e57– e60.

George J, Goldstein E, Abashidze S, Deutsch V, Shmilovich H, Finkelstein A, Herz I, Miller H, Keren G., (2004). Circulating endothelial progenitor cells in patients with unstable angina: association with systemic inflammation. Eur Heart J., 25:1003–1008.

George, J., Goldstein, E., Abashidze, S., Wexler, D., Hamed, S., Shmilovich, H., et al. (2005). Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner. Cardiovasc Res 68(2), 299-306.

George J, Shmilovich H, Deutsch V, Miller H, Keren G, Roth A. (2006). Comparative Analysis of Methods for Assessment of Circulating Endothelial Progenitor Cells, Tissue Engineering 12 (2) 331-335

Gerhard-Herman M, et al. (2002). Assessment of endothelial function (nitric oxide) at the tip of a finger. Circulation, 106:Suppl II:170.

Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, Witte L, Girardi L, Yurt R, Himel H, Rafii S, (2001). Vascular trauma induces rapid but transient mobilization of VEGFR2/AC133 endothelial precursor cells. Circ Res., 88:167–174.

Goon, P.K.Y. Lip G.Y.H, Boos, CJ, Stonelake, PS, Blann, AD. (2006). Circulating Endothelial Cells, Endothelial Progenitor Cells, and Endothelial Microparticles in Cancer, Neoplasia, 8:79-88.

Griese DP, Ehsan A, Melo LG, Kong D, Zhang L, Mann MJ, Pratt RE, Mulligan RC, Dzau VJ, (2003). Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts: implications for cell-based vascular therapy. Circulation, 108: 2710–2715.

Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C, Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler, (2003). Erythropoietin is a potent physiological stimulus for endothelial progenitor cell mobilization. Blood, 102:1340 –1346.

Heeschen C, Lehman R, Honold J, Assmus B, Aicher A, Walter DH, Martin H, Zeiher AM, Dimmeler S. (2004). Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease.Circulation, 109:1615–1622.

Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S., (2002). Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell;109: 625-637.

Hiasa K, Ishibashi M, Ohtani K, Inoue S, Zhao Q, Kitamoto S, Sata M, Ichiki T, Takeshita A, Egashira K. Gene transfer of stromal cell-derived factor 1 enhances ischemic vasculogenesis and angiogenesis via vascular endothelial growth factor/endothelial nitric oxide synthaserelated pathway: next generation chemokine therapy for therapeutic neovascularization. Circulation, 109:2454 –2461.

Hill JM, Zalos G, Halcox JPG, Schenke WH, Waclawin MA, Quyyumi A, Finkel T. (2003). Circulating endothelial progenitor cells, vascular function and cardiovascular risk. N Engl J Med., 348:593– 600.

Hillebrands J-L, Klatter FA, van DijK WD, Rozing J. (2003). Bone marrow does not contribute substantially to endothelial-cell replacement in transplant arteriosclerosis.Nat Med., 8:194 –195.

Hu Y, Davison F, Zhan Z, Xu Q. (2003). Endothelial replacement and angiogenesis in arteriosclerotic lesions of allografts are contributed by circulating progenitor cells.Circulation, 108:3122–3127.

Hur, J., Yoon, C.H., Kim, H.S., Choi, J.H., Kang, H.J., Hwang, K.K., et al. (2004). Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol 24(2), 288–293.

Imanishi, T., Hano, T. & Nishio, I. (2005) Estrogen reduces endothelial progenitor cell senescence through augmentation of telomerase activity. J Hypertens 23(9):1699-1706.

Iwaguro H, Yamaguchi J, Kalka C, Murasawa S, Masuda H, Hayashi S, Silver M, Li T, Isner JM, Asahara T, (2002). Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation, 105:732–738.

Kalka C, Tehrani H, Laudernberg B, Vale P, Isner JM, Asahara T, Symes JF, (2000a). Mobilization of endothelial progenitor cells following gene therapy with VEGF165 in patients with inoperable coronary disease. Ann Thorac Surg., 70:829–834.

Kalka C, Masuda H, Takahashi T, Gordon R, Tepper O, Gravereaux E, Pieczek A, Iwaguro H, Hayashi S-I, Isner JM, Asahara T (2000b). Vascular endothelial growth factor165 gene transfer augments circulating endothelial progenitor cells in human subjects. Circ Res., 86:1198 –1202.

Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M, Li T, Isner JM, Asahara T, (2000c). Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A. 97:3422–3427.

Kang H-J, Kim H-S, Zhang S-Y, Park K-W, Cho H-J, Koo B-K, Kim Y-J, Lee DS, Sohn D-W, Han K-S, Oh B-H, Lee M-M, Park Y-B, (2004). Effects of intracoronary infusion of peripheral blood stem cells mobilized with granulocyte-colony stimulating factor on left ventrricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomized clinical trial. Lancet, 363:751–756.

Kawamoto A, Gwon H-C, Iwaguro H, Yamaguchi J, Uchida S, Masuda H, Silver M, Ma H, Kearney M, Isner JM, Asahara T, (2001). Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation, 103:634–637.

Khan SS, Solomon MA, and McCoy JP Jr, (2005). Detection of circulating-  endothelial cells and endothelial progenitor cells by flow cytometry. Cytometry B Clin Cytom64:1–8.

Kiernan, T.(2006). Endothelial progenitor cells in 2006 – Where are we now? http://www.irishheart.ie/iopen24/catalog/pub/Heartwise/2006/Spring/endothelial.pdf retrieved 6/22/2006. Link not found 5/1/2013

Kim, DH, Leu, HB, Ott, HC & Taylor, DO, Bertolini, F, Mancuso, P & Kerbel, RS, Boos, CJ, Goon, PKY, Lip, GYH, (2005). Multiple comments – Correspondence to the Editor on Circulating Endothelial Progenitor Cells. NEJM, 353:24, 2613-2616

Kleinman, ME, Blei, F, Gurtner, GC, (2005). Circulating Endothelial Progenitor Cells and Vascular Anomalies, Lymphatic Research and Biology, 3;4: 234-239.

Kocher AA, Schuster MD, Szabolcs MJ, Burkhoff D, Wang J, Homma S, Edwards NM, Itescu S. (2001). Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med., 7:430–436.

Kong D, Melo LG, Gnecchi M, Zhang L, Mostoslavski G, Liew CC, Pratt RE, Dzau VJ. (2004a). Cytokine-induced mobilization of circulating endothelial progenitor cells enhances repair of injured arteries. Circulation, 110:2039 –2046.

Kong D, Melo LG, Mangi AA, Zhang L, Lopez-Ilasaca M, Perrella MA, Liew CC, Pratt RE, Dzau VJ, (2004b). Enhanced inhibition of neointimal hyperplasia by genetically engineered endothelial progenitor cells. Circulation, 109:1769 –1775.

Kuvin JT, et al. (2003a). Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J, 146:168-74.

Kuvin JT, et al. (2003b). Peripheral arterial tonometry during hyperemia is blunted in patients with coronary artery disease. J Am Coll of Cardiology, 41:Suppl:269A.

Lapidot T, and Petit, I (2002) Current understanding of stem cell mobilization: The roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Experimental Hematology, 30:973–98

Laufs U, Werner N, Link A, Endres M, Wassmann S, Jurgens K, Miche E, Bohm M, and Nickenig G (2004). Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. Circulation 109: 220–226.

Llevadot J, Murasawa S, Kureishi Y, Uchida S, Masuda H, Kawamoto A, Walsh K, Isner JM, Asahara T, (2001). HMG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells. J Clin Invest., 108:399–405.

Lloyd-Jones, D. and Tian, L. (2006). Predicting Cardiovascular Risk, So What Do We Do Now?. Arch Intern. Med, 166, 1342-1343.

Loomans CJM, de Koening EJP, Staal FJT, Rookmaaker MB, Verseyden C, de Boer HC, Verhaar MC, Braam B, Rebelink TJ, van Zonneveld A-J. (2004). Endothelial progenitor cell dysfunction. A novel concept in the pathogenesis of vascular complications of type I diabetes. Diabetes, 53:195–199.

Losordo DW, Isner JM, Diaz-Sandoval LJ, (2003). Endothelial Recovery. The next target in restenosis prevention. Circulation, 107:2635–2637.

Lusis, A.J. (2000). Atherosclerosis. Nature 407(6801), 233–241. DIGITAL LINK N/A

Massa M, Rosti V, Ferrario M, Campanelli R, Ramajoli, Rosso R, De Ferrari GM, Ferlini M, Goffredo L, Bertoletti A, Klersy C, Pecci A, Moratti R, Tavazzi, (2005). Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction. Blood,105:199 –206.

Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. (2001). Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci U S A. 98:10344 –10349.

Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MA, and Rafii S (2000). Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors. Blood 95: 952–958.

Perin EC, Dohmann HFR, Borojevic R, Silva SA, Sousa AL, Mesquita CT, Rossi MI, Carvalho AC, Dutra HS, Dohmann HJ, Silva GV, Belem L, Vivacqua R, Rangel FO, Esporcatte R, Geng YJ, Vaughn WK, Assad JA, Mesquita ET, Willerson JT, (2003). Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation, 107:2294 –2302.

Powell TM, Paul JD, Hill JM, Thompson M, Benjamin M, Rodrigo M, McCoy JP, Read EJ, Khuu HM, (2005). Leitman SF, Finkel T, Cannon RO III. Granulocyte colony stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease. Arterioscler Thromb Vasc Biol., 25:1– 6.

Rafii S, Lyden D (2003). Therapeutic stem and progenitor cell transplantation for organ vascularisation and regeneration. Nat Med 9: 702–712.

Rauscher FM, Goldschmidt-Clermont PJ, Davis BH, Wang T, Gregg D, Ramaswami P, Pippen AM, Annex BH, Dong C, Taylor DA, (2003). Aging, progenitor cell exhaustion, and atherosclerosis. Circulation, 108:457–463.

Ross R. (1999). Atherosclerosis – An inflammatory disease. N Engl J Med., 340:115–126.

Rubanyi GM. (1993). The role of endothelium in cardiovascular homeostasis and diseases. J Cardiovasc Pharmacol., 22(Suppl):S1–S4.

Sata M, Saiura A, Kunisato A, Tojo A, Okada S, Tokuhisa T, Hirai H, Makuuchi M, Hirata Y, Nagai R. (2002). Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med., 8:403– 409.

Schachinger V, Assmus B, Britten MB, Honold J, Lehman R, Teupe C, Abolmaali ND, Vogt TJ, Hofmann WK, Martin H, Dimmeler S, Zeiher AM, (2004). Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction: final one-year results of the TOPCARE-AMI trial. J Am Coll Cardiol., 44:1690 –1699.

Schatteman GC, Hanlon HD, Jiao C, Dodds SG, Christy BA. (2000). Blood derived angioblasts accelerate blood flow restoration in diabetic mice. J Clin Invest., 106:571–578.

Scheubel RJ, Zorn H, Rolf-Edgar S, Kuss O, Morawietz, Holtz J, Simm A. (2003). Age-dependent depression in circulating endothelial progenitor cells in patients undergoing coronary artery bypass grafting. J Am Col Cardiol., 42:2073–2080.

Segal, M.S., Shah, R., Afzal, A., Perrault, C.M., Chang, K., Schuler, A., et al. (2006). Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes. Diabetes 55(1), 102-109

Shi Q, Raffi, Wu MH, Wijelath ES, Yu C, Ishida A, Fujita Y, Kothari S, Mohle R, Sauvage LR, Moore MAS, Storb RF, Hammond WP. (1998). Evidence of circulating bone-marrow derived endothelial cells. Blood, 92:362–367.

Shi Q, Bhattacharya V, Hong-De Wu M, Sauvage LR. (2002). Utilizing granulocyte colony-stimulating factor to enhance vascular graft endothelialization from circulating blood cells. Ann Vasc Surg., 16:314 –320.

Shintani S, Murohara T, Ikeda H, Ueni T, Honma T, Katoh A, Sasaki K, Shimada T, Oike Y, Imaizumi T, (2001). Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation, 103:2776 –2779.

Shirota, T., Yasui, H., Shimokawa, H. & Matsuda, T. (2003). Fabrication of endothelial progenitor cell (EPC)-seeded intravascular stent devices and in vitro endothelialization on hybrid vascular tissue. Biomaterials 24(13), 2295–2302.

Simper D, Wang S, Deb A, Holmes D, McGregor C, Frantz R, Kushawa SS, Caplice NM, (2003). Endothelial progenitor cells are decreased in blood of cardiac allograft patients with vasculopathy and endothelial cells of non cardiac origin are enriched in transplant atherosclerosis. Circulation, 107:143–149.

Spyridopoulos I, Haendeler J, Urbich C, Brummendorf TH, Oh H, Schneider MD, Zeiher AM, Dimmeler S, (2004). Statins enhance migratory capacity by upregulation of the telomere repeat-binding factor TRF2 in endothelial progenitor cells. Circulation, 110:3136 –3142.

Stamm C, Westphal B, Kleine H-D, Petzsch M, Kittner C, Klinge H, Schumichen C, Nienaber CA, Freund M, Steinhoff G, (2003). Autologous bonemarrow transplantation for myocardial regeneration. Lancet, 361:45–46.

Strauer BE, Brehm M, Zeus T, Kostering M, Hernandez A, Sorg RV, Kogler G, Wernet P, (2002). Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation, 106:1913–1918.

Strehlow K, Werner N, Berweiler J, Link A, Dirnagl U, Priller J, Laufs K, Ghaeni L, Milosevic M, Bohm M, Nickenig G, (2003). Estrogen increases bone-marrow derived endothelial progenitor cell production and diminishes neointima formation.Circulation, 107:3059 –3065.

Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T, (1999). Ischemia- and cytokine-induced mobilization of bone-marrow-derived endothelial progenitor cells for neovascularization. Nat Med., 5:434–438.

Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobwotiz GR, Levine JP, Gurtner GC. (2002). Human endothelial progenitor cells from type II diabetes exhibit impaired proliferation, adhesion, and incorporation into vascular structures.Circulation, 106:2781–2786.

Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, and Lau CP (2003). Angiogenesis in ischaemic myocardium by intramyocardial autologous bone genesis marrow mononuclear cell implantation. Lancet 361: 47–49.

Tung, R, Kaul, S, Diamond, GA, Shah, PK (2006). Drug-Eluting Stents for the Management of Restenosis: A Critical Appraisal of the Evidence. Annals of Internal Medicine, 144;12: 913-919.

Valenzuela-Fernandez A, Planchenault T, Baleux F, et al. (2002) Leukocyte elastase negatively regulates stromal cell-derived factor-1 (SDF)/CXCR4 binding and functions by amino-terminal processing of SDF-1 and CXCR4.  J Biol Chem 277:156

Valgimigli M, Rigolin GM, Fucili A, Della Porta M, Soukhomovskaia O, Malagutti P, Bugli AM, Bragottu LZ, Francolini G, Mauro E, Castoldi G, Ferrari R, (2004). CD34 and endothelial progenitor cells in patients with various degrees of congestive heart failure. Circulation, 110:1209–1212.

Vasa M, Fichtlscherer S, Adler K, Aicher A, Martin H, Zeiher AM, Dimmeler S. (2001a). Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation, 103:2885–2890.

Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S. (2001b). Number and migratory activity of circulating endothelial progenitor cells inversely correlates with risk factors for coronary artery disease. Circ Res., 89:e1– e7.

Vasan, RS, (2006). Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations, Circulation, 113:2335-2362.

Verma S, Kukiszewski MA, Li S-H, Szmitko PE, Zucco L, Wang C-H, Badiwala MV, Mickle DAG, Weisel RD, Fedak PWM, Stewart DJ, Kutrik MJB, (2004). C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function.Circulation, 109:r91–r100.

Verma, S. and Marsden, P.A. (2005). Nitric Oxide-Eluting Polyurethanes – Vascular Grafts of the Future? New England Journal Medicine, 353 (7), 730-731.

Verma S, Szmitko, PE, (2006). The vascular biology of peroxisome proliferator-activated receptors: Modulation of atherosclerosis. Can J Cardiol, 22 (Suppl B):12B-17B.

Walter DH, Rittig K, Bahlmann FH, Kirchmair R, Silver M, Murayama T, Nishimura H, Losordo DW, Asahara T, Isner JM, (2002). Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation, 105:3017–3024.

Werner N, Junk S, Laufs L, Link A, Walenta K, Bohm M, Nickenig G., (2003).  Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury. Circ Res., 93:e17– e24.

Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Böhm M, Nickenig G. (2005a). Circulating Endothelial Progenitor Cells and Cardiovascular Outcomes,NEJM, 353: 999-1007

Werner, N & Nickenig, G. (2005b). Authors Reply to Correspondence to the Editor on Circulating Endothelial Progenitor Cells. NEJM, 353:24, 2613-2616

Widlansky ME, et al. (2003). The clinical implications of endothelial dysfunction. J Am Coll of Cardiology, 42:1149-60.

Wollert KC, Meyer GP, Latz J, Ringes-Lichtenberg S, Lippolt P, Breindenbach C, Fichtner S, Korte T, Hornig B, Messinger D, Arseniev L, Hartenstein B, Ganser A, Drexler H (2004). Intracoronary autologous bonemarrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet, 364:141–148.

Yamaguchi J, Kusano KF, Masuo O, Kawamoto A, Silver M, Murasawa S, Bosch-Marce M, Masuda H, Losordo DW, Isner JM, Asahara T. (2003).  Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation, 107:1322–1328.

Yoon YS, Park JS, Tkebuchava T, Luedeman C, Losordo DW. (2004). Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction. Circulation, 109:3154 –3157.

 

 

Read Full Post »