EFFECTS OF ENDOTHELINS ON COLLAGEN TURNOVER IN CARDIAC FIBROBLASTS
EFFECTS OF ENDOTHELINS ON COLLAGEN TURNOVER IN CARDIAC FIBROBLASTS
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DOI：
10.1093/cvr/27.12.2130
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发表时间：
1993-12-01
影响因子：
10.8
通讯作者：
WEBER, KT
中科院分区：
文献类型：
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作者：
GUARDA, E;KATWA, LC;WEBER, KT
目的：内皮素(ET-1和ET-3)可能是组织重塑的促进剂，包括纤维状胶原堆积。验证了ET-1和ET-3各自影响心脏成纤维细胞胶原转化的假设。方法：成年大鼠心脏成纤维细胞在含0.4%胎牛血清和不同浓度ET-1、ET-3的培养液中培养24小时。用H-3-Pro掺入法检测胶原合成。采用酶联免疫吸附试验(ELISA)检测I型和III型胶原的合成。用酶谱法检测内皮素对胶原酶活性的影响。结果：ET-1和ET-3以浓度依赖的方式促进胶原合成，最大增加1.7倍(P<；0.001 v对照细胞)。ET(A)受体拮抗剂FED-3512-PI(10(-6)M)不阻断ET-1或ET-3对胶原合成的影响。ET-1和ET-3均能显著促进I型和III型胶原的合成(P<0.01)。ET-1使胶原酶活性降低5.8倍(P<；0.01V对照)，这种作用可被FED-3512-PI(10(-6)M)阻断。ET-3不改变胶原酶活性。结论：ET-1和ET-3促进I型和胶原合成，ET-1而不是ET-3降低胶原酶活性。内皮素对心脏成纤维细胞胶原合成的影响可能是通过ET(A)和ET(B)受体介导的，而它们对胶原酶的影响似乎是通过ET(A)受体介导的。
Objectives: Endothelins (ET-1 and ET-3) may be promoters of tissue remodelling, including fibrillar collagen accumulation. The hypothesis that ET-1 and ET-3 each modify cardiac fibroblast collagen turnover was tested. Methods: Confluent adult rat cardiac fibroblasts were maintained for 24 hours in medium with 0.4% fetal calf serum, and varying concentrations of ET-1 or ET-3. Collagen synthesis was measured by H-3-proline incorporation. The synthesis of type I and III collagens was measured by enzyme linked immunosorbent assay (ELISA). The effects of endothelins on collagenase activity were estimated by zymography. Results: ET-1 and ET-3 increased collagen synthesis in a concentration-dependent manner with a maximal 1.7-fold increase (p < 0.001 v control cells). The effects of ET-1 or ET-3 on collagen synthesis were not blocked by FED-3512-PI (10(-6) M), an ET(A) receptor antagonist. ET-1 and ET-3 each significantly (p < 0.01) increased the synthesis of both type I and III collagens. ET-1 caused a 5.8-fold decrease in collagenase activity (p < 0.01 v control), and this effect was blocked by FED-3512-PI (10(-6) M). ET-3 did not alter collagenase activity. Conclusion: ET-1 and ET-3 increased the synthesis of type I and In collagens, whereas ET-1, but not ET-3, reduced collagenase activity. The effects of endothelins on collagen synthesis in cardiac fibroblasts seem to be mediated through ET(A) and ET(B) receptors, whereas their effects on collagenase seem to be mediated by ET(A) receptors.