Why is coronary collateral growth impaired in type II diabetes and the metabolic syndrome?
1Department of Biochemistry and Molecular Biology, University of South Alabama College of Medicine, Mobile, AL 36688, United States. procic@usouthal.edu
Abstract:
Type II diabetes and the metabolic syndrome are strong predictors of severity of occlusive coronary disease and poorer outcomes of coronary revascularization therapies. Coronary collateral growth can provide an alternative or accessory pathway of revascularization. However, collateral growth is impaired in type II diabetes and the metabolic syndrome. Although many factors necessary for collateral growth are known and many interventions have shown promising results in animal studies, not a single attempt to induce coronary collateral growth in human clinical trials has led to satisfactory results. Accordingly, the first part of this review outlines the known deleterious effects of diabetes and the metabolic syndrome on factors necessary for collateral growth, including pro-angiogenic growth factors, endothelial function, the redox state of the coronary circulation, intracellular signaling, leukocytes and bone marrow-derived progenitors cells. The second section highlights the gaps in our current knowledge of how these factors interact with the radically altered environment of the coronary circulation in diabetes and the metabolic syndrome. The interplay between these pathologies and inadequately explored areas related to the temporal regulation of collateral remodeling and the roles of the extracellular matrix, vascular cell phenotype and pro-inflammatory cytokines are emphasized with implications to development of efficient therapies.
Insights
Type II diabetes impairs coronary collateral growth, hindering revascularization. Understanding these detrimental effects is crucial for developing effective therapies for patients with coronary disease.
Area of Science:
- Cardiovascular Medicine
- Metabolic Diseases
- Regenerative Medicine
Background:
- Type II diabetes and metabolic syndrome predict severe coronary artery disease and poor outcomes after revascularization.
- Coronary collateral growth is a compensatory mechanism but is significantly impaired in these conditions.
- Current therapies to induce collateral growth have shown limited success in human trials.
Purpose of the Study:
- To review the detrimental effects of diabetes and metabolic syndrome on factors essential for coronary collateral growth.
- To identify knowledge gaps regarding the interaction of these pathologies with the coronary circulation.
- To highlight areas for future therapeutic development.
Main Methods:
- Review of existing literature on diabetes, metabolic syndrome, and coronary collateralization.
- Analysis of factors affecting collateral growth, including growth factors, endothelial function, and cellular components.
- Identification of research gaps in temporal regulation, extracellular matrix, and inflammatory roles.
Main Results:
- Diabetes and metabolic syndrome negatively impact pro-angiogenic factors, endothelial function, redox balance, and progenitor cell activity.
- Significant gaps exist in understanding how these factors interact within the altered coronary environment.
- Inadequately explored areas include temporal regulation of remodeling, extracellular matrix, cell phenotype, and cytokines.
Conclusions:
- Diabetes and metabolic syndrome present multifaceted challenges to coronary collateral growth.
- Further research is needed to elucidate the complex interplay of factors and temporal dynamics in collateral remodeling.
- Targeting these specific molecular and cellular pathways holds promise for future therapeutic strategies.
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