Angiogenesis of the heart

Michael J B Kutryk1, Duncan J Stewart

  • 1Division of Cardiology, Terrence Donnelly Heart Center, St. Michael's Hospital, University of Toronto, Toronto M5B 1W8, Ontario, Canada. kutrykm@smh.toronto.on.ca

Insights

Therapeutic angiogenesis offers a novel treatment for coronary artery disease patients unsuitable for traditional procedures. This approach uses growth factors to stimulate new blood vessel growth, creating natural bypasses.

Area of Science:

  • Cardiovascular Medicine
  • Regenerative Medicine
  • Molecular Biology

Background:

  • Coronary artery disease (CAD) remains a leading cause of mortality, with many patients ineligible for standard revascularization (angioplasty, stenting, CABG).
  • A significant unmet need exists for alternative treatment strategies for these patients.

Purpose of the Study:

  • To review therapeutic angiogenesis as a promising treatment for CAD.
  • To explore gene and protein-based therapies aimed at promoting new blood vessel formation.

Main Methods:

  • Discussion of key growth factors (VEGF, FGF, Ang) involved in angiogenesis, vasculogenesis, and arteriogenesis.
  • Examination of gene therapy vectors, protein delivery methods, and desired therapeutic outcomes.
  • Identification of quantifiable clinical endpoints for evaluating angiogenesis trials.

Main Results:

  • Preclinical studies indicate therapeutic angiogenesis is feasible and effective.
  • Further research is required to address remaining questions regarding clinical application.

Conclusions:

  • Therapeutic angiogenesis, utilizing growth factors via gene or protein therapy, presents a potential new avenue for treating patients with coronary artery disease.
  • This strategy aims to develop endogenous bypass vessels to improve blood flow in ischemic regions.

Related Concept Videos

Anatomy of the Heart01:27

Anatomy of the Heart

The human heart is made up of three layers of tissue that are surrounded by the pericardium, a membrane that protects and confines the heart. The outermost layer, closest to the pericardium, is the epicardium. The pericardial cavity separates the pericardium from the epicardium. Beneath the epicardium is the myocardium, the middle layer, and the endocardium, the innermost layer. There are four chambers of the heart: the right atrium, the right ventricle, the left atrium, and the left ventricle.
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Development of the Heart01:27

Development of the Heart

The development of the human heart, a crucial organ, commences from the mesoderm on the 18th or 19th day after fertilization. This process initiates in the cardiogenic area, a group of mesodermal cells at the embryo's head end, which evolves into elongated strands known as cardiogenic cords. These cords undergo a transformation to form hollow-centered endocardial tubes.
As the embryo undergoes lateral folding, these paired tubes approach each other, merging into a single primitive heart tube by...
Development of Blood Vessels01:07

Development of Blood Vessels

The development of the vascular system in a fetus is a complex and intricate process that begins as early as 15 to 16 days post-conception. This process starts outside the embryo, specifically in the mesoderm of the yolk sac, chorion, and connecting stalk. Approximately two days later, the formation of blood vessels occurs within the embryo itself.
The initial formation of this system is facilitated by the small amount of yolk present in the ovum and yolk sac. Blood vessels originate from...
Anatomy of the Heart01:20

Anatomy of the Heart

The heart is a hollow, muscular organ approximately the size of a fist, consisting of four chambers. It is enclosed in the pericardium, a fibrous sac with two layers: the visceral and parietal pericardium, separated by a fluid-filled space containing serous fluid to reduce friction.
The heart has three layers: the innermost endocardium, the muscular myocardium, and the outer epicardium, all working together for optimal cardiac function.
Chambers of the Heart
The heart is made up of four...