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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 Sep;84(3):1005–1012. doi: 10.1172/JCI114221

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

C A Tozzi 1, G J Poiani 1, A M Harangozo 1, C D Boyd 1, D J Riley 1
PMCID: PMC329748  PMID: 2668338

Abstract

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.

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