Pressure-induced connective tissue synthesis in pulmonary artery segments is dependent on intact endothelium.

Pressure-induced connective tissue synthesis in pulmonary artery segments is dependent on intact endothelium.
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肺动脉段中压力诱导的结缔组织合成依赖于完整的内皮。

DOI:
10.1172/jci114221
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发表时间:
1989
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Riley,DJ
Riley,DJ
中科院分区:
--
文献类型:
--
作者:
Tozzi,CA;Poiani,GJ;Harangozo,AM;Boyd,CD;Riley,DJ

文献摘要

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肺血管重构中结缔组织积累的生理刺激尚不明确。我们假设肺动脉中心动脉内压力的增加是结缔组织合成的刺激,而这种反应依赖于完整的内皮。将相当于50 mmHg压力的机械张力施加于离体大鼠肺动脉(内皮完整或去除)4小时,测量[14C]脯氨酸融入胶原、[14C]缬氨酸融入弹性蛋白、[3H]胸苷融入DNA和前α - 1 (I)胶原mRNA水平。在完整血管中,张力诱导胶原蛋白(3.1 +/- 0.4 vs. 2.3 +/- 0.5 [SEM] dpm X 10(2) [14C]-羟脯氨酸/[mg protein.h]) (n = 10)和弹性蛋白(6.1 +/- 2.4 vs. 2.9 +/- 0.4 dpm X 10(3) [14C]缬氨酸/[mg protein.h]) (n = 5)的合成(P均小于0.05)。前α 1 (I)胶原的稳态mRNA水平也因张力升高(46比30 × 10(2) dpm杂交/100 ng总RNA)。然而,刺激并没有增加[3H]胸苷并入DNA。在脱落的血管中,张力对结缔组织合成和前α 1 (I)胶原mRNA水平没有影响。v-sis的信使RNA水平在完整而非剥落的血管中被张力诱导。我们的研究结果表明,机械张力诱导血管结缔组织合成依赖于完整的内皮。图片
Physiologic stimuli of connective tissue accumulation in pulmonary vascular remodeling are poorly defined. We postulated that increased pressure within central pulmonary arteries is a stimulus for connective tissue synthesis and the response is dependent on an intact endothelium. Mechanical tension equivalent to 50 mmHg pressure was applied for 4 h to isolated rat main pulmonary arteries (endothelium intact or removed), and incorporation of [14C]proline into collagen, [14C]valine into elastin, [3H]thymidine into DNA and pro alpha 1 (I) collagen mRNA levels were measured. In intact vessels, tension induced synthesis of collagen (3.1 +/- 0.4 vs. 2.3 +/- 0.5 [SEM] dpm X 10(2) [14C]-hydroxyproline/[mg protein.h]) (n = 10) and elastin (6.1 +/- 2.4 vs. 2.9 +/- 0.4 dpm X 10(3) [14C]valine/[mg protein.h]) (n = 5) (both P less than 0.05). Steady state mRNA levels of pro alpha 1 (I) collagen were also increased by tension (46 vs. 30 X 10(2) dpm hybridized/100 ng total RNA). However, the stimulus did not increase [3H]thymidine incorporation into DNA. In denuded vessels, tension had no effect on connective tissue synthesis or mRNA level of pro alpha 1 (I) collagen. Messenger RNA levels for v-sis were induced by tension in intact but not denuded vessels. Our findings establish that induction of vascular connective tissue synthesis by mechanical tension is dependent on an intact endothelium.Images