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Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
Published on: June 14, 2016
Extracellular Matrix Protein Ratios in the Human Heart and Vessels: How to Distinguish Pathological From
Corey Wittig1, Robert Szulcek1
1Laboratory of in vitro Modeling Systems of Pulmonary Diseases, Institute of Physiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Insights
Cardiovascular diseases alter heart and vessel extracellular matrix (ECM) protein ratios, specifically collagen-I/collagen-III and elastin/collagen. These changes impact tissue biomechanics and function.
Area of Science:
- Biochemistry
- Cardiovascular Biology
- Biomaterials Science
Background:
- Extracellular matrix (ECM) proteins, primarily collagen-I, collagen-III, and elastin, are crucial for cardiac and vascular tissue biomechanics.
- Changes in the relative content and ratios of these ECM proteins are hallmarks of cardiovascular pathology and aging.
Purpose of the Study:
- To review alterations in collagen-I/collagen-III and elastin/collagen ratios in cardiovascular diseases and aging.
- To discuss the structure, function, and turnover of major cardiovascular ECM proteins.
- To guide in vitro modeling by focusing on human heart and aorta ECM.
Main Methods:
- Literature review focusing on cardiovascular diseases including aging, dilated cardiomyopathy, coronary artery disease, atrial fibrillation, aortic aneurysms, atherosclerosis, and hypertension.
- Analysis of ECM protein quantification methodologies and inter-study comparability.
- Examination of ECM protein ratios in human heart and aorta tissues.
Main Results:
- Cardiovascular diseases tend to increase collagen-I relative concentration, leading to higher collagen-I/collagen-III ratios.
- Elastin/collagen ratios generally decrease in cardiovascular disease states.
- Distinct pathological states correlate with specific ranges on a continuous scale of ECM protein ratios, with significant differences between heart and aorta.
Conclusions:
- Altered ECM protein ratios are indicative of specific cardiovascular pathologies and aging.
- Understanding these ratio shifts is vital for interpreting tissue biomechanics and developing in vitro models.
- Methodological considerations in ECM quantification are important for accurate comparative studies.
Abstract:
Cardiovascular pathology is often accompanied by changes in relative content and/or ratios of structural extracellular matrix (ECM) proteins within the heart and elastic vessels. Three of these proteins, collagen-I, collagen-III, and elastin, make up the bulk of the ECM proteins in these tissues, forming a microenvironment that strongly dictates the tissue biomechanical properties and effectiveness of cardiac and vascular function. In this review, we aim to elucidate how the ratios of collagen-I to collagen-III and elastin to collagen are altered in cardiovascular diseases and the aged individuum. We elaborate on these major cardiovascular ECM proteins in terms of structure, tissue localization, turnover, and physiological function and address how their ratios change in aging, dilated cardiomyopathy, coronary artery disease with myocardial infarction, atrial fibrillation, aortic aneurysms, atherosclerosis, and hypertension. To the end of guiding in vitro modeling approaches, we focus our review on the human heart and aorta, discuss limitations in ECM protein quantification methodology, examine comparability between studies, and highlight potential in vitro applications. In summary, we found collagen-I relative concentration to increase or stay the same in cardiovascular disease, resulting in a tendency for increased collagen-I/collagen-III and decreased elastin/collagen ratios. These ratios were found to fall on a continuous scale with ranges defining distinct pathological states as well as a significant difference between the human heart and aortic ECM protein ratios.
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