CONNECTIVE-TISSUE AND REPAIR IN THE HEART - POTENTIAL REGULATORY MECHANISMS
CONNECTIVE-TISSUE AND REPAIR IN THE HEART - POTENTIAL REGULATORY MECHANISMS
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DOI：
10.1111/j.1749-6632.1995.tb17438.x
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发表时间：
1995-01-01
期刊：
影响因子：
--
通讯作者：
ZHOU, GP
中科院分区：
文献类型：
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作者：
WEBER, KT;SUN, Y;ZHOU, GP
心脏由高度分化的心肌细胞和间质或结缔组织组成，心肌细胞构成实质。特别是心脏及其瓣膜小叶中的原纤维胶原周转是动态的，对组织修复至关重要。新出现的证据进一步表明，结缔组织是一种代谢活性实体，其中肽激素产生和降解，反过来，这些肽调节胶原蛋白的周转。这一概念起源于定量体外放射自显影术，使用赖诺普利的碘化衍生物（125 I-351 A）作为配体定位心脏内的血管紧张素转换酶（ACE）结合密度。一个不均匀的分布被发现：低密度的ACE结合在心房和心室内，高ACE结合密度的高胶原周转的网站，如瓣叶，外膜，和纤维组织的不同病因的起源。ACE产生细胞在这些后者的网站被确定的单克隆ACE抗体。它们包括瓣膜间质细胞（维克）和成纤维细胞样细胞，每种细胞也含有α-平滑肌肌动蛋白和I型胶原蛋白的转录物（原位杂交）。发现培养的维克中的底物利用包括血管紧张素I和缓激肽。在维克和纤维组织部位观察到血管紧张素II和缓激肽受体-配体结合。结缔组织ACE不依赖于循环血管紧张素II。在体内，纤维组织形成通过ACE抑制或AT 1受体拮抗而减弱。血管紧张素II和缓激肽是刺激和抑制，分别培养的成人心脏成纤维细胞胶原蛋白的合成，这表明一个范例的相互调节成纤维细胞胶原蛋白的周转。基质及其细胞成分代表了一个动态的代谢实体，调节其自身的肽激素组成和纤维胶原蛋白的周转。这些发现可能提供的见解，可用于促进或阻止纤维组织形成取决于心血管疾病的性质。
The heart is composed of highly differentiated cardiac myocytes, which constitute parenchyma, and stroma or connective tissue. Fibrillar collagen turnover in the heart and its valve leaflets, in particular, is dynamic and essential to tissue repair. Emerging evidence further suggests connective tissue is a metabolically active entity, where peptide hormones are generated and degraded and, in turn, these peptides regulate collagen turnover. This concept arose from quantitative in vitro autoradiography using an iodinated derivative of lisinopril (125I-351A) as ligand to localize angiotensin converting enzyme (ACE) binding density within the heart. A heterogeneous distribution was found: low-density ACE binding within atria and ventricles; high ACE binding density at sites of high collagen turnover, such as valve leaflets, adventitia, and fibrous tissue of diverse etiologic origins. ACE-producing cells at these latter sites were identified by monoclonal ACE antibody. They included valvular interstitial cells (VIC) and fibroblast-like cells each of which also contained alpha-smooth muscle actin and the transcript for type I collagen (in situ hybridization). Substrate utilization in cultured VIC was found to include angiotensin I and bradykinin. Angiotensin II and bradykinin receptor-ligand binding was observed in VIC and at fibrous tissue sites. Connective tissue ACE is independent of circulating angiotensin II. In vivo, fibrous tissue formation is attenuated by ACE inhibition or antagonism of AT1 receptor. Angiotensin II and bradykinin are stimulatory and inhibitory, respectively, to cultured adult cardiac fibroblast collagen synthesis suggesting a paradigm of reciprocal regulation to fibroblast collagen turnover. Stroma and its cellular constituents represent a dynamic metabolic entity that regulates its own peptide hormone composition and turnover of fibrillar collagen. These findings may provide insights that could be used to advantage to either promote or forestall fibrous tissue formation depending on the nature of cardiovascular disease.