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Vasculogenesis and angiogenesis: extracellular matrix remodeling in coronary collateral arteries and the ischemic
1Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Insights
Coronary collateral vessel development involves matrix proteinases and antiproteinases. Understanding these factors in vascular remodeling may lead to new treatments for ischemic heart disease.
Area of Science:
- Cardiovascular Biology
- Vascular Remodeling
- Extracellular Matrix Dynamics
Background:
- Ischemic cardiomyopathy is a leading cause of heart failure and cardiovascular mortality.
- Collateral circulation is crucial for supplying oxygen to ischemic myocardium.
- Vascular remodeling involves extracellular matrix synthesis and degradation, regulated by proteinases and antiproteinases.
Purpose of the Study:
- To review the role of extracellular matrix proteinases and antiproteinases in vascular remodeling and collateral development.
- To highlight new information impacting the understanding of vascular extracellular matrix turnover.
- To identify potential pharmacological targets for enhancing collateral formation.
Main Methods:
- Review of existing literature on coronary collateral development.
- Analysis of the role of matrix proteinases and antiproteinases in vascular remodeling.
- Examination of a canine model of chronic coronary artery occlusion.
Main Results:
- Collateral vessel remodeling involves dynamic changes in extracellular matrix components.
- The balance between proteinases and antiproteinases is critical for adaptive changes during collateral development.
- Extracellular matrix components play a significant role in coronary collateral vessel formation.
Conclusions:
- Matrix proteinases and antiproteinases are key players in the mechanisms of collateral development.
- Understanding these mechanisms can inform the development of therapies to improve myocardial blood flow.
- Targeting extracellular matrix turnover offers potential for treating ischemic heart disease.
Abstract:
Heart failure secondary to ischemic cardiomyopathy is the primary cause of cardiovascular mortality. The promise of the collateral circulation lies in its potential to alter the course of the natural history of coronary heart disease. The collateral circulation of the heart is responsible for supplying blood and oxygen to the myocardium at ischemic risk following severe stenosis and reduced vasoelasticity function of a major coronary artery. In response to flow, stress, and pressure, collateral vessels are restructured and remodeled. Vascular remodeling by its very nature implies synthesis and degradation of extracellular matrix components in the vessel wall. Under normal physiological conditions proteinases that break down the specialized matrix are tightly regulated by antiproteinases. The balance between proteinase and antiproteinase influences is discoordinated during collateral development which leads to adaptive changes in the structure, function, and regulation of extracellular matrix components in the vessel wall. The role of extracellular matrix components in coronary collateral vessel formation in a canine model of chronic coronary artery occlusion has been demonstrated. The role of matrix proteinases and antiproteinases in the collateral vessel play a significant role in the underlying mechanisms of collateral development. This review presents new and significant information regarding the role of extracellular matrix proteinases and antiproteinases in vascular remodeling, function, and collateral development. Such information will have a significant impact on the understanding of the basic biology of the vascular extracellular matrix turnover, remodeling, and function as well as on elucidating potential avenues for pharmacological approaches designed to increase collateral formation and optimize myocardial blood flow in the treatment of ischemic heart disease.