Secretion of endothelin-1 and endothelin-3 by human cultured vascular smooth muscle cells.

摘要: 1. It is generally accepted that endothelial cells secrete endothelin (ET) to the underlying media which mediates contractile effects of ET. However, there some evidence animal vascular smooth muscle (VSMCs) also We cultured VSMCs from human vessels representative a number different beds determine whether endogenously 2. explanted adult arterial picomolar quantities immunoreactive mature ET: coronary artery 226.6 +/- 58.8 pM/10(6) (n = 7), thoracic aorta 169.5 105.4 3), left internal mammary 102.4 23.1 3) and saphenous vein 69.4 19.9 as well umbilical (HUVSMCs) 38.3 4.3 3). Secretion big ET-1 was detected: 249.1 59.4 120.0 13.4 170.0 68.2 105.1 30.7 146.3 7.4 Comparable, intracellular levels ET were detected in VSMCs. 3. Since enzyme-dispersed are thought be more differentiated closely resemble their vivo counterparts, these secreted greatest peptides, they characterized further. Reverse transcription-polymerase chain reaction assay demonstrated HUVSMCs express mRNA. High performance liquid chromatography coupled radioimmunoassay revealed ET-3, addition ET-1. not altered by 100 AM phosphoramidon,an inhibitor metalloproteases or microM pepstatin A, an aspartyl protease inhibitor.4. In concordance, KD Bmax values for [125I]-ET-l saturation binding HUVSMC cultures incubated 24 h with phosphoramidon (431 218 PM 31.1 12.7 fmol mg-1;mean =/- s.e.mean, n A (381 169PM 7.8 mg-1, compared controls (355 99 pM 33.3 9.3 mg-1; This observation indicates absence autocrine 'unmasking' effect receptors.5. synthesize ET-1, ET-3 possess There common cellular mechanisms between growth factors vasoconstrictor suggesting close relationship contraction proliferation. development various pathologies such atherosclerosis, hypertension after vessel injury has been attributed alterations normal pattern VSMCs, role diseases may significance.