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Posts Tagged ‘Cardiovascular Risk Reduction’

Introduction to e-Series A: Cardiovascular Diseases, Volume Four Part 2: Regenerative Medicine


Introduction to e-Series A: Cardiovascular Diseases, Volume Four Part 2: Regenerative Medicine

Author and Curator: Larry H Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN

This document is entirely devoted to medical and surgical therapies that have made huge strides in

  • simplification of interventional procedures,
  • reduced complexity, resulting in procedures previously requiring surgery are now done, circumstances permitting, by medical intervention.

This revolution in cardiovascular interventional therapy is regenerative medicine.  It is regenerative because it is largely driven by

  • the introduction into the impaired vasculature of an induced pleuripotent cell, called a stem cell, although
  • the level of differentiation may not be a most primitive cell line.

There is also a very closely aligned development in cell biology that extends beyond and including vascular regeneration that is called synthetic biology.  These developments have occurred at an accelerated rate in the last 15 years. The methods of interventional cardiology were already well developed in the mid 1980s.  This was at the peak of cardiothoracic bypass surgery.

Research on the endothelial cell,

  • endothelial cell proliferation,
  • shear flow in small arteries, especially at branch points, and
  • endothelial-platelet interactions

led to insights about plaque formation and vessel thrombosis.

Much was learned in biomechanics about the shear flow stresses on the luminal surface of the vasculature, and there was also

  • the concomitant discovery of nitric oxide,
  • oxidative stress, and
  • the isoenzymes of nitric oxide synthase (eNOS, iNOS, and nNOS).

It became a fundamental tenet of vascular biology that

  • atherogenesis is a maladjustment to oxidative stress not only through genetic, but also
  • non-genetic nutritional factors that could be related to the balance of omega (ω)-3 and omega (ω)-6 fatty acids,
  • a pro-inflammatory state that elicits inflammatory cytokines, such as, interleukin-6 (IL6) and c-reactive protein(CRP),
  • insulin resistance with excess carbohydrate associated with type 2 diabetes and beta (β) cell stress,
  • excess trans- and saturated fats, and perhaps
  • the now plausible colonic microbial population of the gastrointestinal tract (GIT).

There is also an association of abdominal adiposity,

  • including the visceral peritoneum, with both T2DM and with arteriosclerotic vessel disease,
  • which is presenting at a young age, and has ties to
  • the effects of an adipokine, adiponectin.

Much important work has already been discussed in the domain of cardiac catheterization and research done to

  • prevent atheroembolization.and beyond that,
  • research done to implant an endothelial growth matrix.

Even then, dramatic work had already been done on

  • the platelet structure and metabolism, and
  • this has transformed our knowledge of platelet biology.

The coagulation process has been discussed in detailed in a previous document.  The result was the development of a

  • new class of platelet aggregation inhibitors designed to block the activation of protein on the platelet surface that
  • is critical in the coagulation cascade.

In addition, the term long used to describe atherosclerosis, atheroma notwithstanding, is “hardening of the arteries”.  This is particularly notable with respect to mid-size arteries and arterioles that feed the heart and kidneys. Whether it is preceded by or develops concurrently with chronic renal insufficiency and lowered glomerular filtration rate is perhaps arguable.  However, there is now a body of evidence that points to

  • a change in the vascular muscularis and vessel stiffness, in addition to the endothelial features already mentioned.

This has provided a basis for

  • targeted pharmaceutical intervention, and
  • reduction in salt intake.

So we have a  group of metabolic disorders, which may alone or in combination,

  • lead to and be associated with the long term effects of cardiovascular disease, including
  • congestive heart failure.

This has been classically broken down into forward and backward failure,

  • depending on decrease outflow through the aorta (ejection fraction), or
  • decreased venous return through the vena cava,

which involves increased pulmonary vascular resistance and decreased return into the left atrium.

This also has ties to several causes, which may be cardiac or vascular. This document, as the previous, has four pats.  They are broadly:

  1. Stem Cells in Cardiovascular Diseases
  2. Regenerative Cell and Molecular Biology
  3. Therapeutics Levels In Molecular Cardiology
  4. Research Proposals for Endogenous Augmentation of circulating Endothelial Progenitor Cells (cEPCs)

As in the previous section, we start with the biology of the stem cell and the degeneration in cardiovascular diseases, then proceed to regeneration, then therapeutics, and finally – proposals for augmenting therapy with circulating endogenous endothelial progenitor cells (cEPCs).

 

context

stem cells

 

theme

regeneration

 

 

 

 

theme

Therapeutics

 

theme

augmentation

 

 

 

 

 

 

 

 

 

 

Key pathways involving NO

Key pathways involving NO

 

 

 

 

stem cell lin28

stem cellLlin28

1479-5876-10-175-1-l  translational research with feedback loops

Tranlational Research -Lab to Bedside

 

 

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Heart Rate Variability (HRV) as a Tool

Reporter and Curator: Larry H. Bernstein, MD, FCAP

The article that follows expands on the discussions about exercise, walking or running, and burning calories, an adjunct to good nutrition.  It elucidates how monitoring of performance in physical conditioning is done by monitoring the heart rate variability.  The fact is that outside of concussion injuries that may take a toll in time, or even cause a subdural hematoma, there are “silent” events that are related to sudden death.  These are serious cardiovascular events.

Heart Rate Variability (HRV) as a Tool for Diagnostic and Monitoring Performance in Sport and Physical Activities

Journal of Exercise Physiology  Jun 2013; 15(3):103-131.  ISSN 1097-9751

B Makivic, M Djordjevic, MS Willis

1Center for Sport Science and University Sport, University of Vienna, Vienna, Austria, 2Faculty of Sport and Physical Education, Belgrade, Serbia, 3McAllister Heart Institute, University of North Carolina, Medical Biomolecular Research Building, Chapel Hill, NC.

The dynamic autonomic responses during exercise can be measured

  • to give actionable information for training
  • by analysis of the ECG to determine heart rate variability (HRV).

While application of HRV has been applied to

  • predict sudden cardiac death and diabetic neuropathy
  • in assessing disease progression,

recent studies have suggested that it may be applied to exercise training. In this review, we present

  • the rationale for measuring HRV.

We describe the

  • different variables used and
  • what they can tell us about the autonomic nervous system.

The use of HRV in detecting changes in exercise intensity is presented, along with evidence that

  • gender and age changes may affect autonomic HRV.

Lastly, we illustrate how

  • HRV measurements taken immediately post-exercise have proven to be useful
  • in measuring and monitoring training load to proscribe workouts and/or prevent over-training.

Despite the studies that

  • vary widely in their application to different training levels of athletes being tested and
  • HRV measures used,

the standardization of methodologies and results should help accelerate the use of HRV in sports training.
Key Words: Autonomic Nervous System; Overtraining; HRV

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Macrovascular Disease – Therapeutic Potential of cEPCs: Reduction Methods for CV Risk

Curator: Aviva Lev-Ari, PhD, RN

An Investigation of the Potential of circulating Endothelial Progenitor Cells (cEPCs) as a Therapeutic Target for Pharmacological Therapy Design for Cardiovascular Risk Reduction: A New Multimarker Biomarker Discovery

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