Reversal of Cardiac mitochondrial dysfunction
Curator: Larry H Bernstein, MD, FACP
This article is the FOURTH in a four-article Series covering the topic of the Roles of the Mitochondria in Cardiovascular Diseases. They include the following;
- Mitochondria and Cardiovascular Disease: A Tribute to Richard Bing, Larry H Bernstein, MD, FACP
http://pharmaceuticalintelligence.com/2013/04/14/chapter-5-mitochondria-and-cardiovascular-disease/
- Mitochondrial Metabolism and Cardiac Function, Larry H Bernstein, MD, FACP
http://pharmaceuticalintelligence.com/2013/04/14/mitochondrial-metabolism-and-cardiac-function/
- Mitochondrial Dysfunction and Cardiac Disorders, Larry H Bernstein, MD, FACP
http://pharmaceuticalintelligence.com/2013/04/14/mitochondrial-dysfunction-and-cardiac-disorders/
- Reversal of Cardiac mitochondrial dysfunction, Larry H Bernstein, MD, FACP
http://pharmaceuticalintelligence.com/2013/04/14/reversal-of-cardiac-mitochondrial-dysfunction/
Mitochondrial metabolism and cardiac function
There is sufficient evidence to suggest that, even with optimal therapy, there is an
- attenuation or loss of effectiveness of neurohormonal antagonism as heart failure worsens.
The production of oxygen radicals is increased in the failing heart, whereas
- normal antioxidant enzyme activities are preserved.
Mitochondrial electron transport is an enzymatic source of oxygen radical generation and
- can be a therapeutic target against oxidant-induced damage in the failing myocardium.
Therefore, future therapeutic targets
- must address the cellular and molecular mechanisms that contribute to heart failure.
Furthermore, since fundamental characteristics of the failing heart are
- defective mitochondrial energetics and
- abnormal substrate metabolism
we might expect that substantial benefit may be derived from the development of therapies aimed at
- preserving cardiac mitochondrial function and
- optimizing substrate metabolism.
Nutrition and physiological function
- decreased superoxide production and
- preserved oxidative phosphorylation in cardiac mitochondria,
- decreased myocardial damage.
- in endothelial function but
- no improvement in skeletal muscle energy metabolism.
- appear to preserve mitochondrial function
- improving cardiac energy metabolism and
- function in rats with chronic heart failure.
- levels of the mitochondrial biogenesis transcription factors PPARg coactivator-1a and
- nuclear respiratory factor-2a, and
- prevented mitochondrial dysfunction
- decreased oxidative stress and
- improved endothelial function,
- stimulate mitochondrial biogenesis and
- improve energy metabolism.
- existing cardioprotective agents require further investigation.
Substrate metabolism in the failing heart
- elevating plasma FFA concentrations.
- fatty acids are ligands for the peroxisome proliferator-activated receptors (PPARs),
- members of the nuclear hormone receptor (NHR) family.
- acyl-CoA synthetase,
- carnitine palmitoyltransferase (CPT)-1,
- long-chain acyl-CoA dehydrogenase, and
- uncoupling protein (UCP)3.
- increasing oxygen consumption for any given workload.
- from the inherent stoichiometric inefficiency of fatty acid oxidation,
- which accounts for the consumption of 12% more oxygen per ATP synthesized than glucose oxidation.
High levels of plasma FFAs have been associated with increased cardiac UCP3 levels in patients undergoing CABG(Fig) and
- are believed to activate the uncoupling action of UCP3.
http://htmlimg1.scribdassets.com/8o5pfgywg0lyerj/images/4-244729cb6a.jpg
- free fatty acid (FFA) uptake via the carnitine palmitoyltransferase (CPT) system with perhexiline,
- giving rise to more oxygen-efficient glucose oxidation.
- synthesized from cytosolic acetyl-CoA by acetyl-CoA carboxylase.
- malonyl-CoA decarboxylase, which normally converts malonyl-CoA back to acetyl-CoA,
- elevates malonyl-CoA levels, inhibiting mitochondrial FFA uptake and thus protects the failing heart.
Nutritional Support for the Mitochondria
Human Studies Animal or In Vitro Studies
Alpha lipoic acid Resveratrol
Co-Enzyme Q10 EgCG
Acetyl-L-Carnitine Curcumin
Lipoic Acid & Acetyl-L-Carnitine
Alpha lipoic acid is known to be a mitochondrial antioxidant that preserves or improves mitochondrial function.
- lipoic acid can prevent arterial calcification, and
- arterial calcification may be related to mitochondrial dysfunction
- methods are under study to increase lipoic acid synthase production, the enzyme responsible for making lipoic acid in the body.
Co-Enzyme Q10
It is well known that statin drugs taken for high cholesterol severely reduce CoQ10 levels, and causes other negative cardiovascular side effects.
A study on CAD patients has shown that over 8 weeks of supplementing with 300mg of CoQ10 reversed
- mitochondrial dysfunction (as measured by a reduced lactate:pyruvate ratio) and
- improved endothelial function (as measured by increased flow-mediated dilation)
Other Mitochondrial Antioxidants
Other natural compounds that have been shown to have antioxidant effects in the mitochondria include
- resveratrol, found in wine and grapes,
- curcumin from turmeric and
- EGCG, found abundantly in green tea extract.
But no studies have been conducted for these compounds in CVD.
Metabolic syndrome and serum carotenoids: findings of a cross-sectional study
in Queensland, Australia
Metabolic syndrome and serum carotenoids.
- diabetes and
- cardiovascular disease,
- antioxidant nutrients may play a protective role in these conditions.
- atherosclerosis,
- stroke,
- hypertension,
- certain cancers,
- inflammatory diseases and
- diabetic retinopathy.
The primary carotenoids found in human serum are
- α-carotene
- β-carotene
- β-cryptoxanthin
- lutein/zeaxanthin
- lycopene.
- Weight
- height
- BMI
- waist circumference
- blood pressure
- fasting and 2-34 hour blood glucose
- lipids
- five serum carotenoids.
Components = 0 -none of the metabolic syndrome components (i.e. abdominal obesity, raised triglyceride,
- Components = any 1 one of the five metabolic syndrome components is present ;
- Components = 2 – any two of the five components are present;
- Components = 3 any three of the components are present;
- Components = 4 – any four of the components are present;
- Components = 5 = all five metabolic syndrome components are present.
- age
- sex
- education
- BMI
- smoking
- alcohol intake
- physical activity
- vitamin use.
- alpha-carotene,
- beta carotene and
- the sum of five carotenoids
- body mass index
- waist circumference
- systolic and diastolic blood pressure
- blood lipids.
- age group, smoking status, educational status and income.
- inverse relationship between vegetable intake (not fruit) and serum carotenoids.
- compared to those who consumed 1 serve or less of vegetables.
- with the metabolic syndrome present compared with those without the syndrome, after adjusting for potential confounding variables.
- the number of components of the metabolic syndrome increased after adjusting for potential confounding variables.
- individual and total serum carotenoids and metabolic syndrome status and each of its components.
- α-carotene,
- β-carotene and
- the sum of the five carotenoids
- the number of the metabolic syndrome components increased.
- α-carotene,
- β-carotene,
- β-cryptoxanthin
- total carotenoids.
(not lycopenes)
Carnitine: A novel health factor-An overview.
- obtained in greater amount from animal dietary sources than from plant sources.
- liver
- kidney
- brain
- dependent on iron, vitamin C, niacin, pyridoxine .
- through in vivo synthesis than omnivorous subjects.
- plays a significant role in regulating the carnitine biosynthesis.
- the balance between the rate of synthesis and rate of excretion
- through specific transporter proteins.
- carnitine transport proteins and
- transport into mitochondrial matrix.
- for β-oxidation, thereby, generating ATP.
- present on the plasma membrane of liver and kidney and
- also due to dysfunction of carnitine reabsorbtion through
- similar transport proteins in renal tubules.
- mitochondrial disorders and also
- defective β-oxidation such as CPT-II and acyl CoA dehydrogenase.
Propionyl-L-carnitine Corrects Metabolic and Cardiovascular Alterations in
Diet-Induced Obese Mice and Improves Liver Respiratory Chain Activity
but not the increase in free fatty acid, triglyceride and HDL/LDL ratio induced by high-fat diet.
Vehicle-HF exhibited a reduced
- cardiac output/body weight ratio,
- endothelial dysfunction and
- tissue decrease of NO production,
all of them being improved by PLC treatment.
The decrease of hepatic mitochondrial activity by high-fat diet was reversed by PLC.
decreases the cardiovascular risk associated with the metabolically impaired mitochondrial function.
Omega-3 Fatty Acid and cardioprotection
The Benefits of Flaxseed
By Elaine Magee, MPH, RD WebMD Expert Column
Some call it one of the most powerful plant foods on the planet. There’s some evidence it may help reduce your risk of
- heart disease, cancer, stroke, and diabetes.
That’s quite a tall order for a tiny seed that’s been around for centuries.
Flaxseed was cultivated in Babylon as early as 3000 BC. In the 8th century, King Charlemagne believed so strongly in the
health benefits of flaxseed that he passed laws requiring his subjects to consume it. Now, thirteen centuries later, some
experts say we have preliminary research to back up what Charlemagne suspected.
http://img.webmd.com/dtmcms/live/webmd/consumer_assets/site_images/article_
thumbnails/features/benefits_of_flaxseed_features/375x321_benefits_of_flaxseed_features.jpg
Not only has consumer demand for flaxseed grown, agricultural use has also increased.
Flaxseed is what’s used to feed all those chickens that are laying eggs with higher levels of omega-3 fatty acids.
Although flaxseed contains all sorts of healthy components, it owes its primary healthy reputation to three of them:
- Omega-3 essential fatty acids, have been shown to have heart-healthy effects. 1.8 grams of plant omega-3s/tablespoon ground.
- Lignans, which have both plant estrogen and antioxidant qualities. 75 to 800 times more lignans than other plant foods.
- Fiber. Flaxseed contains both the soluble and insoluble types.
Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Diseases
- herring, mackerel, salmon, albacore tuna, and sardines, or
- by consuming fish oil supplements or cod liver oil.
- that are the original source of the omega-3 polyunsaturated fatty acids (ω-3 PUFA) found in fish oils.
- fish oil consumption decreases the risk of major cardiovascular (CV) events, such as
- myocardial infarction (MI),
- sudden cardiac death (SCD),
- coronary heart disease (CHD),
- atrial fibrillation (AF), and most recently,
- death in patients with heart failure (HF).
- eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the long-chain fatty acids in this family.
- the plant-based precursor of EPA.
- at a dose of approximately 1 g/day of combined DHA and EPA, either in the form of fatty fish or fish oil supplements
- particularly in secondary prevention of cardiovascular (CV) diseases.
- in the primary and secondary prevention of various CV disorders.
- of nearly 40,000 participants randomized to receive eicosapentaenoic acid (EPA)
- with or without docosahexaenoic acid (DHA) in studies of patients
- in primary prevention,
- after myocardial infarction, and
- with heart failure (HF).
Background Epidemiologic Evidence
- Antiarrhythmic effects
- Improvements in autonomic function
- Decreased platelet aggregation
- Vasodilation
- Decreased blood pressure
- Anti-inflammatory effects
- Improvements in endothelial function
- Plaque stabilization
- Reduced atherosclerosis
- Reduced free fatty acids and triglycerides
- Up-regulated adiponectin synthesis
- Reduced collagen deposition
- and at least 800 to 1,000 mg/day for individuals with known coronary heart disease and HF.
- provides maximal cardioprotection in those at risk of CV disease
- as well in the treatment of atherosclerotic, arrhythmic, and primary myocardial disorders.
Assessing Appropriateness of Lipid Management Among Patients With Diabetes Mellitus
- potentially leading to adverse events and unnecessary costs.
- to encourage appropriate treatment with moderate-dose statins while minimizing over-treatment.
- having a low-density lipoprotein (LDL) <100 mg/dL,
- taking a moderate-dose statin regardless of LDL level or measurement, or
- receiving appropriate clinical action (starting, switching, or intensifying statin therapy) if LDL is ≥100 mg/dL.
- without ischemic heart disease who were on a high-dose statin.
- 67.2% with LDL <100 mg/dL,
- 13.0% with LDL ≥100 mg/dL and either on a moderate-dose statin (7.5%) or with appropriate clinical action (5.5%), and
- 4.4% with no index LDL on at least a moderate-dose statin. Of the entire cohort ≥18 years of age, 13.7% were potentially over-treated.
- are receiving appropriate dyslipidemia management.
Exercise training and mitochondria in heart failure
- exercise capacity,
- quality of life,
- hospitalization rates and
- morbidity/mortality.
- mitochondrial function, and
- no modification of myocardial oxidative capacity,
- oxidative enzymes, or
- energy transfer enzymes
- ventricular remodelling,
- restored contractile function and
- improved intracellular calcium handling.
- skeletal muscle oxidative capacity with
- increased mitochondrial density
- exercise intolerance and
- chronic fatigue.
- more effective peripheral oxygen delivery following training,
- alleviating tissue hypoxia and oxidative stress.
Treating Type 2 diabetes, and lowering cardiovascular disease risk
Treating Diabetes and Obesity with an FGF21-Mimetic Antibody
Activating the βKlotho/FGFR1c Receptor Complex
IN Foltz, S Hu, C King, Xinle Wu, et al. Amgen and Texas A&M HSC, Houston, TX.
Sci Transl Med Nov 2012; 4(162), p. 162ra153
http://dx.doi.org/10.1126/scitranslmed.3004690
Fibroblast growth factor 21 (FGF21) is a distinctive member of the FGF family with potent beneficial effects on
- lipid
- body weight
- glucose metabolism
A monoclonal antibody, mimAb1, binds to βKlotho with high affinity and specifically
- activates signaling from the βKlotho/FGFR1c (FGF receptor 1c) receptor complex.
Injection of mimAb1 into obese cynomolgus monkeys led to FGF21-like metabolic effects:
- decreases in body weight,
- plasma insulin,
- triglycerides, and
- glucose during tolerance testing.
Mice with adipose-selective FGFR1 knockout were refractory to FGF21-induced improvements
- in glucose metabolism and body weight.
mimAb1 depends on βKlotho to activate FGFR1c, but
- it is not expected to induce side effects caused by activating FGFR1c alone.
The results in obese monkeys (with mimAb1) and in FGFR1 knockout mice (with FGF21) demonstrated
- the essential role of FGFR1c in FGF21 function and
- suggest fat as a critical target tissue for the cytokine and antibody.
This antibody activates FGF21-like signaling through cell surface receptors, and provided
- preclinical validation for an innovative therapeutic approach to diabetes and obesity.
Influencing Factors on Cardiac Structure and Function Beyond Glycemic Control
in Patients With Type 2 Diabetes Mellitus (T2DM)
R Ichikawa, M Daimon, T Miyazaki, T Kawata, et al. Cardiovasc Diabetol. 2013;12(38)
We studied 148 asymptomatic patients with T2DM without overt heart disease.
Early (E) and late (A) diastolic mitral flow velocity and early diastolic mitral annular velocity (e’)
- were measured for assessing left ventricular (LV) diastolic function.
In addition
- insulin resistance,
- non-esterified fatty acid,
- high-sensitive CRP,
- estimated glomerular filtration rate,
- waist/hip ratio,
- abdominal visceral adipose tissue (VAT),
- subcutaneous adipose tissue (SAT)
In T2DM (compared to controls),
- E/A and e’ were significantly lower, and
- E/e’, left atrial volume and LV mass were significantly greater
VAT and age were independent determinants of
- left atrial volume (β =0.203, p=0.011),
- E/A (β =−0.208, p=0.002), e’ (β =−0.354, p<0.001) and
- E/e’ (β=0.220, p=0.003).
Independent determinants of LV mass were
- systolic blood pressure,
- waist-hip ratio (β=0.173, p=0.024)
- VAT/SAT ratio (β=0.162, p=0.049)
Excessive visceral fat accompanied by adipocyte dysfunction may play a greater role than
- glycemic control in the development of diastolic dysfunction and LV hypertrophy in T2DM
Inhibition of oxidative stress and mtDNA damage
Novel pharmacological agents are needed that
- optimize substrate metabolism and
- maintain mitochondrial integrity,
- improve oxidative capacity in heart and skeletal muscle, and
- alleviate many of the clinical symptoms associated with heart failure.
The evidence for the attenuation or loss of effectiveness of neurohormonal antagonism as heart failure worsens
- indicates future therapeutic targets must address the cellular and molecular mechanisms that contribute to heart failure.
Pharmacological Targets of oxidative stress and mitochondrial damage
Defective mitochondrial energetics and abnormal substrate metabolism are fundamental characteristics of CHF.
A significant benefit may be derived from developing therapies aimed at
- preserving cardiac mitochondrial function and
- optimizing substrate metabolism.
- with preserved antioxidant enzyme activities suggests
- mitochondrial electron transport as a source of oxygen radical generation
- can be a therapeutic target against oxidant-induced damage in the failing myocardium.
- leads to mitochondrial DNA (mtDNA) damage,
- functional decline,
- further oxygen radical generation, and
- cellular injury.
- development and progression of myocardial remodelling and failure.
- myocyte hypertrophy,
- apoptosis, and
- interstitial fibrosis
- by activating matrix metallo-proteinases,
- promoting the development and
- progression of maladaptive myocardial remodelling and failure.
- may activate integral signalling molecules in myocardial remodelling and failure (Figure).
- hypertrophy and apoptosis in isolated cardiac myocytes.
- peroxiredoxin-3 (Prx-3), a mitochondrial antioxidant, or
- mitochondrial transcription factor A (TFAM),
- could ameliorate the decline in mtDNA copy number in failing hearts.
- decrease in mitochondrial function was prevented,
- proving that the activation of Prx-3 or TFAM gene expression
- could ameliorate the pathophysiological processes seen
- in mitochondrial dysfunction and
- myocardial remodelling.
- could be novel and effective treatment strategies for heart failure.
- mitochondrial transcription factor A (TFAM) gene prevents
- mitochondrial DNA (mtDNA) damage,
- oxidative stress, and
- myocardial remodelling and failure.
- directly interacts with mitochondrial DNA to form nucleoids.
- increases the production of reactive oxygen species (ROS)
- leading to a catastrophic cycle of mitochondrial electron transport impairment,
- further reactive oxygen species generation, and mitochondrial dysfunction.
- directly binding and stabilizing mitochondrial DNA and
- increasing the steady-state levels of mitochondrial DNA
Conclusion
- abnormal energetics and substrate metabolism in heart and skeletal muscle.
- elevated fatty acid levels,
- tissue hypoxia and oxidative stress and
- metabolic modulation of heart and skeletal muscle mitochondria,
- appears to offer a promising therapeutic strategy for tackling heart failure.
References
Mitochondrial dynamics and cardiovascular diseases Ritu Saxena
http://pharmaceuticalintelligence.com/2012/11/14/mitochondrial-dynamics-and-cardiovascular-diseases/
Mitochondrial Damage and Repair under Oxidative Stress larryhbern
http://pharmaceuticalintelligence.com/2012/10/28/mitochondrial-damage-and-repair-under-oxidative-stress/
Mitochondria: Origin from oxygen free environment, role in aerobic glycolysis, metabolic adaptation larryhbern
http://pharmaceuticalintelligence.com/2012/09/26/mitochondria-origin-from-oxygen-free-environment-role-in-aerobic-glycolysis-metabolic-adaptation/
Ca2+ signaling: transcriptional control larryhbern
http://pharmaceuticalintelligence.com/2013/03/06/ca2-signaling-transcriptional-control/
MIT Scientists on Proteomics: All the Proteins in the Mitochondrial Matrix identified Aviva Lev-Ari
http://pharmaceuticalintelligence.com/2013/02/03/mit-scientists-on-proteomics-all-the-proteins-in-the-mitochondrial-matrix-identified/
Nitric Oxide has a ubiquitous role in the regulation of glycolysis -with a concomitant influence on mitochondrial function larryhbern
http://pharmaceuticalintelligence.com/2012/09/16/nitric-oxide-has-a-ubiquitous-role-in-the-regulation-of-glycolysis-with-a-concomitant-influence-on-mitochondrial-function/
Ubiquinin-Proteosome pathway, autophagy, the mitochondrion, proteolysis and cell apoptosis larryhbern
http://pharmaceuticalintelligence.com/2013/02/14/ubiquinin-proteosome-pathway-autophagy-the-mitochondrion-proteolysis-and-cell-apoptosis-reconsidered/
Low Bioavailability of Nitric Oxide due to Misbalance in Cell Free Hemoglobin in Sickle Cell Disease – A Computational Model Anamika Sarkar
http://pharmaceuticalintelligence.com/2012/11/09/low-bioavailability-of-nitric-oxide-due-to-misbalance-in-cell-free-hemoglobin-in-sickle-cell-disease-a-computational-model/
The rationale and use of inhaled NO in Pulmonary Artery Hypertension and Right Sided Heart Failure larryhbern
http://pharmaceuticalintelligence.com/2012/08/20/the-rationale-and-use-of-inhaled-no-in-pulmonary-artery-hypertension-and-right-sided-heart-failure/
Mitochondria and Cardiovascular Disease: A Tribute to Richard Bing, Larry H Bernstein, MD, FACP
http://pharmaceuticalintelligence.com/2013/04/14/chapter-5-mitochondria-and-cardiovascular-disease/
Mitochondrial Metabolism and Cardiac Function, Larry H Bernstein, MD, FACP
http://pharmaceuticalintelligence.com/2013/04/14/mitochondrial-metabolism-and-cardiac-function/
Mitochondrial Dysfunction and Cardiac Disorders, Larry H Bernstein, MD, FACP
http://pharmaceuticalintelligence.com/2013/04/14/mitochondrial-dysfunction-and-cardiac-disorders/
Reversal of Cardiac mitochondrial dysfunction, Larry H Bernstein, MD, FACP
http://pharmaceuticalintelligence.com/2013/04/14/reversal-of-cardiac-mitochondrial-dysfunction/
Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination? Aviva Lev-Ari, PhD, RN 10/19/2012
http://pharmaceuticalintelligence.com/2012/10/19/clinical-trials-results-for-endothelin-system-pathophysiological-role-in-chronic-heart-failure-acute-coronary-syndromes-and-mi-marker-of-disease-severity-or-genetic-determination/
Endothelin Receptors in Cardiovascular Diseases: The Role of eNOS Stimulation, Aviva Lev-Ari, PhD, RN 10/4/2012
http://pharmaceuticalintelligence.com/2012/10/04/endothelin-receptors-in-cardiovascular-diseases-the-role-of-enos-stimulation/
Inhibition of ET-1, ETA and ETA-ETB, Induction of NO production, stimulation of eNOS and Treatment Regime with PPAR-gamma agonists (TZD): cEPCs Endogenous Augmentation for Cardiovascular Risk Reduction – A Bibliography, Aviva Lev-Ari, PhD, RN 10/4/2012
http://pharmaceuticalintelligence.com/2012/10/04/inhibition-of-et-1-eta-and-eta-etb-induction-of-no-production-and-stimulation-of-enos-and-treatment-regime-with-ppar-gamma-agonists-tzd-cepcs-endogenous-augmentation-for-cardiovascular-risk-reduc/
Genomics & Genetics of Cardiovascular Disease Diagnoses: A Literature Survey of AHA’s Circulation Cardiovascular Genetics, 3/2010 – 3/2013, L H Bernstein, MD, FACP and Aviva Lev-Ari,PhD, RN 3/7/2013
http://pharmaceuticalintelligence.com/2013/03/07/genomics-genetics-of-cardiovascular-disease-diagnoses-a-literature-survey-of-ahas-circulation-cardiovascular-genetics-32010-32013/
Cardiovascular Disease (CVD) and the Role of agent alternatives in endothelial Nitric Oxide Synthase (eNOS) Activation and Nitric Oxide Production, Aviva Lev-Ari, PhD, RN 7/19/2012 http://pharmaceuticalintelligence.com/2012/07/19/cardiovascular-disease-cvd-and-the-role-of-agent-alternatives-in-endothelial-nitric-oxide-synthase-enos-activation-and-nitric-oxide-production/
Cardiovascular Risk Inflammatory Marker: Risk Assessment for Coronary Heart Disease and Ischemic Stroke – Atherosclerosis. Aviva Lev-Ari, PhD, RN 10/30/2012
http://pharmaceuticalintelligence.com/2012/10/30/cardiovascular-risk-inflammatory-marker-risk-assessment-for-coronary-heart-disease-and-ischemic-stroke-atherosclerosis/
Cholesteryl Ester Transfer Protein (CETP) Inhibitor: Potential of Anacetrapib to treat Atherosclerosis and CAD. Aviva Lev-Ari, PhD, RN 4/7/2013
http://pharmaceuticalintelligence.com/2013/04/07/cholesteryl-ester-transfer-protein-cetp-inhibitor-potential-of-anacetrapib-to-treat-atherosclerosis-and-cad/
Hypertriglyceridemia concurrent Hyperlipidemia: Vertical Density Gradient Ultracentrifugation a Better Test to Prevent Undertreatment of High-Risk Cardiac Patients, Aviva Lev-Ari, PhD, RN 4/4/2013 http://pharmaceuticalintelligence.com/2013/04/04/hypertriglyceridemia-concurrent-hyperlipidemia-vertical-density-gradient-ultracentrifugation-a-better-test-to-prevent-undertreatment-of-high-risk-cardiac-patients/
Fight against Atherosclerotic Cardiovascular Disease: A Biologics not a Small Molecule – Recombinant Human lecithin-cholesterol acyltransferase (rhLCAT) attracted AstraZeneca to acquire AlphaCore.
Aviva Lev-Ari, PhD, RN 4/3/2013
http://pharmaceuticalintelligence.com/2013/04/03/fight-against-atherosclerotic-cardiovascular-disease-a-biologics-not-a-small-molecule-recombinant-human-lecithin-cholesterol-acyltransferase-rhlcat-attracted-astrazeneca-to-acquire-alphacore/
High-Density Lipoprotein (HDL): An Independent Predictor of Endothelial Function & Atherosclerosis, A Modulator, An Agonist, A Biomarker for Cardiovascular Risk. Aviva Lev-Ari, PhD, RN 3/31/2013
http://pharmaceuticalintelligence.com/2013/03/31/high-density-lipoprotein-hdl-an-independent-predictor-of-endothelial-function-artherosclerosis-a-modulator-an-agonist-a-biomarker-for-cardiovascular-risk/
Peroxisome proliferator-activated receptor (PPAR-gamma) Receptors Activation: PPARγ transrepression for Angiogenesis in Cardiovascular Disease and PPARγ transactivation for Treatment of Diabetes.
Aviva Lev-Ari, PhD, RN 11/13/2012
http://pharmaceuticalintelligence.com/2012/11/13/peroxisome-proliferator-activated-receptor-ppar-gamma-receptors-activation-pparγ-transrepression-for-angiogenesis-in-cardiovascular-disease-and-pparγ-transactivation-for-treatment-of-dia/
Sulfur-Deficiciency and Hyperhomocysteinemia, L H Bernstein, MD, FACP
http://pharmaceuticalintelligence.com/2013/04/04/sulfur-deficiency-and-hyperhomocusteinemia/
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Structure of the human mitochondrial genome. (Photo credit: Wikipedia)
English: Treatment Guidelines for Chronic Heart Failure (Photo credit: Wikipedia)
English: Oxidative stress process Italiano: Processo dello stress ossidativo (Photo credit: Wikipedia)
Diagram taken from the paper “Dissection of mitochondrial superhaplogroup H using coding region SNPs” (Photo credit: Asparagirl)
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Many thanks,Annette