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Connective tissue: a metabolic entity?
1Department of Internal Medicine, University of Missouri Health Sciences Center, Columbia, USA.
Insights
The heart's connective tissue is metabolically active, regulating peptide hormones that control collagen turnover. This challenges the view of stroma as inert, revealing its dynamic role in cardiac health.
Area of Science:
- Cardiovascular Biology
- Connective Tissue Research
- Molecular Cardiology
Background:
- The heart comprises parenchyma (cardiac myocytes) and stroma (connective tissue).
- Cardiac stroma has been considered metabolically inert, receiving limited research attention.
- Emerging evidence suggests connective tissue plays a more active regulatory role.
Purpose of the Study:
- To investigate the metabolic activity of cardiac connective tissue.
- To explore the role of stroma in regulating peptide hormone generation and degradation.
- To determine if these hormones influence collagen turnover in an autocrine manner.
Main Methods:
- Quantitative in vitro autoradiography using 125I-351A to localize angiotensin-converting enzyme (ACE) binding density.
- Immunohistochemistry with monoclonal ACE antibody.
- In situ hybridization to detect type I collagen transcripts.
- Receptor-ligand binding assays for angiotensin II and bradykinin.
Main Results:
- ACE binding density is heterogeneous in the heart, with high concentrations in areas of high collagen turnover (valve leaflets, adventitia, fibrous tissue).
- ACE activity in these sites is independent of circulating angiotensin II.
- Fibroblast-like cells expressing alpha-actin and type I collagen transcripts produce ACE.
- Angiotensin II and bradykinin receptors are present in fibrous tissue, suggesting autocrine regulation of collagen turnover.
- ACE inhibition or angiotensin II receptor antagonism attenuates connective tissue formation.
Conclusions:
- Cardiac stroma is a dynamic, metabolically active entity, not inert.
- Connective tissue regulates its own peptide hormone composition.
- This regulation influences the turnover of fibrillar collagen in the heart.
Abstract:
The heart is composed of parenchyma (cardiac myocytes) and stroma (connective tissue). Stroma is presumed inert and therefore little attention has been paid to its regulation. Contrary to this notion, evidence presented here raises the possibility that connective tissue is a metabolically active entity capable of regulating peptide hormone generation and degradation and these hormones, in an autocrine manner, regulate collagen turnover. This concept has evolved from quantitative in vitro autoradiography (using 125I-351A), which localized angiotensin converting enzyme (ACE) binding density within the heart. A heterogenous distribution was found. Low-density ACE is present within atria and ventricles. At sites of high collagen turnover, such as valve leaflets, adventitia and fibrous tissue of diverse etiologic origins. ACE binding density is high and independent of circulating angiotensin II. ACE-producing cells at these sites, identified by monoclonal ACE antibody and 125I-351A binding, include fibroblast-like alpha actin-containing cells that express the transcript for type I collagen (in situ hybridization). Receptor-ligand binding for angiotensin II and bradykinin is found in fibrous tissue, where these peptides may provide for a reciprocal regulation of fibroblast collagen turnover. Connective tissue formation is attenuated by ACE inhibition or antagonism of type I angiotensin II receptor. Thus, emerging evidence raises the possibility that stroma and its cellular constituents is a dynamic, metabolically active entity regulating its own peptide hormone composition and, in turn, its turnover of fibrillar collagen.