Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To define the local effects of prostacyclin (PGI2) on the growth of vascular smooth muscle cells (VSMC), we transfected VSMC with an expression vector harboring the cDNA for PGI2 synthase (PGIS), which catalyzes the rearrangement of prostaglandin H2 to PGI2. Transfection of the human PGIS cDNA into rat VSMC did not affect DNA synthesis under serum-free basal conditions, but it increased PGI2 synthesis and decreased DNA synthesis under serum-stimulated conditions (in the presence of 1 or 5% fetal calf serum). These results demonstrated that locally synthesized PGI2 can exert autocrine and/or paracrine inhibitory effects on VSMC growth. It was also suggested that in vivo transfer of PGIS gene may be useful for the gene therapy for vascular disease such as neointimal hyperplasia.
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PMID:Overexpression of prostacyclin synthase inhibits growth of vascular smooth muscle cells. 748 5

Diabetic vascular disease is accompanied by decreased formation of the vasodilators, nitric oxide (NO), and prostacyclin and increased formation of vasoconstrictor eicosanoids, which exacerbate the progression of vascular disease. Similarities between the dysfunction introduced by short-term effects of elevated glucose and long-term effects of diabetes suggest that the alteration in endothelial factors in diabetes primarily results from exposure of endothelial cells to elevated glucose, although undoubtedly hyperlipidemia contributes as well. A key alteration in endothelial cell phenotype is increased formation of reactive oxygen species. This is in part due to uncoupling of endothelial NO synthase such that it generates superoxide anion in addition to NO. This is responsible for NO synthase to produce peroxynitrite, a damaging molecule. Peroxynitrite inactivates prostacyclin synthase leading to the accumulation of inflammatory and prothrombotic eicosanoids. This not only helps to explain the impairment of endothelial vasodilator mechanisms, but also increased progression of vascular disease. Many of these cellular abnormalities can be prevented by adequate scavenging of oxygen-derived free radicals or by blocking the actions of the eicosanoids at thromboxane (TP) receptors. Exposure to elevated glucose also gives rise to oxidants in smooth muscle, and recent studies indicate that oxidation of cysteine thiols under these conditions may prevent physiological NO signaling. As a result, the responsiveness to NO is impaired and accounts in part for abnormal endothelium-dependent vasodilation.
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PMID:Role of nitric oxide in diabetic complications. 1628 Jun 43

The endothelial cells control the tone of the underlying vascular smooth muscle by releasing vasoactive substances. Endothelium-derived relaxing factors (EDRF), in particular nitric oxide have received considerable attention, but much less is known about the ability of the endothelial cells to release endothelium-derived contracting factors (EDCF). The possible players of endothelium-dependent contractions and the underlying mechanisms leading to the release of EDCF will be discussed in the present review. EDCF is likely to consist of two components: 1) prostanoids (including endoperoxides, prostacyclin, thromboxane A(2), and prostaglandin E(2)) and 2) reactive oxygen species. The former directly activate thromboxane/prostaglandin endoperoxide (TP) receptors of the vascular smooth muscle cells which leads to their contraction, while the latter first stimulate the cyclooxygenase in the smooth muscle with subsequent stimulation of the TP receptors by the prostanoids produced. Dysfunction in calcium handling is the leading causal factor for the exacerbated occurrence of endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat (SHR). The observed increased expressions of endothelial COX-1, prostacyclin synthase, thromboxane synthase and enhanced TP receptor sensitivity are not prerequisites for, but intensify the magnitude of endothelium-dependent contractions. Selective TP receptor antagonists are effective in preventing endothelium-dependent contractions in vitro which highlights the prospective use of such drugs in correcting the imbalanced release of endothelium-derived vasoactive substances that accompany vascular disease.
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PMID:Prostanoids and reactive oxygen species: team players in endothelium-dependent contractions. 1928 26