Brilla C G, Zhou G, Rupp H, Maisch B, Weber K T
Molecular Cardiology Laboratory, Philipps University of Marburg, Germany.
Am J Cardiol. 1995 Nov 2;76(13):8D-13D. doi: 10.1016/s0002-9149(99)80485-8.
In hypertensive heart disease, after myocardial infarction or in congestive heart failure, myocardial fibrosis presenting as a diffuse perivascular and interstitial accumulation of fibrillar collagens within the normal connective tissue structures of the myocardium is associated with an activated renin-angiotensin system (RAS). This reactive fibrosis occurs in the overloaded left ventricle and the nonoverloaded right ventricle irrespective of myocyte necrosis or the development of myocyte hypertrophy. Therefore, it appears that hemodynamic factors or the load of the ventricle are not primarily responsible for the adverse fibrous tissue response in the myocardium, and humoral factors may play a key role in regulating the myocardial collagen matrix. The neurohumoral response in hypertensive heart disease, after myocardial infarction with overall deterioration of left ventricular function or congestive heart failure leads to an activation of either the cardiac or the circulating RAS, which closely interacts with the bradykinin-prostaglandin system. To ascertain whether the RAS modulates collagen fibroblasts that express mRNAs for types I and III collagens (the major fibrillar collagens in the heart) and matrix metalloproteinase 1 (MMP1; the key enzyme for collagen degradation), collagen synthesis was measured by [3H]proline incorporation normalized to total protein synthesis and MMP1 activity was determined by degradation of [14C]collagen in cultured fibroblasts after 24-hour incubation with various concentrations of angiotensin II or PGE2 (10(-11)-10(-3) M) under serum-free conditions. In addition, effects of angiotensin II were evaluated in the presence or absence of either type 1 (ICI D8731) or type 2 (PD 123177) angiotensin II (AT1 or PGE2 (10(-11)-10(-3) M) under serum-free conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
在高血压性心脏病、心肌梗死后或充血性心力衰竭中，心肌纤维化表现为心肌正常结缔组织结构内纤维状胶原的弥漫性血管周围和间质积聚，这与肾素 - 血管紧张素系统（RAS）激活有关。这种反应性纤维化发生在负荷过重的左心室和未负荷过重的右心室，与心肌细胞坏死或心肌细胞肥大的发展无关。因此，血流动力学因素或心室负荷似乎并非心肌不良纤维组织反应的主要原因，体液因素可能在调节心肌胶原基质中起关键作用。高血压性心脏病、左心室功能全面恶化的心肌梗死后或充血性心力衰竭中的神经体液反应会导致心脏或循环RAS激活，其与缓激肽 - 前列腺素系统密切相互作用。为确定RAS是否调节表达I型和III型胶原（心脏中的主要纤维状胶原）mRNA的胶原成纤维细胞以及基质金属蛋白酶1（MMP1；胶原降解的关键酶），在无血清条件下，用不同浓度的血管紧张素II或前列腺素E2（10⁻¹¹ - 10⁻³ M）孵育培养的成纤维细胞24小时后，通过将[³H]脯氨酸掺入量标准化为总蛋白合成来测量胶原合成，并通过[¹⁴C]胶原降解来测定MMP1活性。此外，在存在或不存在1型（ICI D8731）或2型（PD 123177）血管紧张素II受体拮抗剂的情况下评估血管紧张素II的作用，以及在无血清条件下用不同浓度的前列腺素E2（10⁻¹¹ - 10⁻³ M）进行评估。（摘要截断于250字）
