1,721,369 research outputs found
Proceedings of the Symposium "Cardiometabolic Risk and Vascular Disease--From Mechanisms to Treatment".
No full text[Statins in cardiovascular disease. Role of Rho/Rho kinase inhibition and of Akt activation ].
No full textStatins are widely used in clinical practice because they are effective in the prevention of cardiovascular events. Most likely, these beneficial effects are due not only to an improved lipid profile bud also to direct vascular actions. Statins inhibit HMG-CoA reductase, which is a rate-limiting enzyme of the mevalonate-cholesterol pathway. Activation of this pathway leeds to the production of intermediates such is all-trans geranyl-geranyl pyrophosphate. This intermediate activates Rho by post-translational modification, a process of which is inhibited by statins. Recent findings on statin-induced inhibition of Rho/Rho-kinase and activation of Akt provide new insights into the protective action of statins in acute coronary syndromes
Abnormalities of endothelial function in the pathogenesis of stroke: the importance of endothelin.
No full textEndothelial cells play a key role in the local regulation of the vascular smooth muscle tone by producing and releasing relaxing and contracting factors. Endothelin (ET)-1, one of the most potent endogenous vasoconstrictor substances known, is produced by endothelial cells. In the cerebral vasculature ET-1 is thought to be involved in several pathological conditions, including vasospasm following subarachnoid hemorrhage and stroke. This review contains evidence suggesting that endothelial dysfunction may contribute to the development of ischemic stroke and discusses the current knowledge concerning the role of ET-1 in the pathogenesis of stroke in animal models and in humans
Hypertension, stroke, and endothelium
No full textEndothelial dysfunction, the complex, multifaceted, pathologic product of various vasculotoxic agents or injuries, is an intermediate attractant phenotype of cardiovascular diseases that usually has a long and unpredictable natural history. Furthermore, endothelial dysfunction may not only represent a vascular disease marker, but actually may play an important pathogenetic role that leads to the progression of the disease and the unfavorable outcomes. Among these vascular diseases, cerebrovascular accidents, particularly stroke, clearly represent a paradigmatic example of the potential role of dysfunctional endothelium. Elevated blood pressure has long been recognized as one of the most important risk factors for stroke; other factors, however, seem to play an important role. Indeed, epidemiologic evidence suggests that, in spite of an improved control of blood pressure, the secular trends of stroke in well-controlled populations are increasing. In this brief review, we analyze current evidence suggesting that endothelial dysfunction can play a role in the pathogenesis of ischemic stroke
Tetrahydrobiopterin and dysfunction of endothelial nitric oxide synthase in coronary arteries.
No full textBACKGROUND:
The L-arginine/nitric oxide pathway plays a key role in the regulation of arterial tone. Biosynthesis of nitric oxide requires activation of nitric oxide synthase in the presence of tetrahydrobiopterin as a cofactor. Biochemical studies demonstrated that activation of purified nitric oxide synthase at suboptimal concentrations of tetrahydrobiopterin leads to production of hydrogen peroxide. The present experiments were designed to determine whether in coronary arteries inhibition of tetrahydrobiopterin synthesis may favor nitric oxide synthase-catalyzed production of hydrogen peroxide.
METHODS AND RESULTS:
Primary branches of canine left anterior descending artery were incubated for 6 hours in minimum essential medium in the presence or in the absence of the tetrahydrobiopterin synthesis inhibitor 2,4-diamino-6-hydroxypyrimidine (DAHP; 10(-2) mol/L). Arterial rings were suspended for isometric tension recording. Production of cGMP was measured by radioimmunoassay. Experiments were performed in the presence of indomethacin (10(-5) mol/L). During contractions to the thromboxane A2/prostaglandin H2 receptor agonist U46619 (10(-7) mol/L), calcium ionophore A23187 (10(-9) to 10(-6) mol/L) caused endothelium-dependent relaxations. A nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (3 x 10(-4) mol/L), significantly inhibited these relaxations. In DAHP-treated arteries, relaxations to A23187 and its stimulating effect on cGMP production were significantly reduced in the presence of catalase (1200 U/mL). By contrast, catalase did not exert any effect in rings incubated in the absence of DAHP. Furthermore, the inhibitory effect of catalase on A23187-induced relaxations was abolished when coronary arteries were incubated in the presence of DAHP plus a liposoluble analogue of tetrahydrobiopterin, 6-methyltetrahydropterin (10(-4) mol/L).
CONCLUSIONS:
The present study suggests that hydrogen peroxide may be a mediator of endothelium-dependent relaxations in coronary arteries depleted of tetrahydrobiopterin. This initially compensatory response, triggered by a dysfunctional nitric oxide synthase, may represent an important mechanism underlying oxidative vascular injury
p66 Shc as the engine of vascular aging.
No full textThe present work is addressing the latest advances made in understanding the molecular mechanisms of vascular aging. Increased production of reactive oxygen species (ROS) is the common denominator of vascular aging, endothelial dysfunction and atherosclerosis. ROS are generated by different intracellular molecular pathways. In view of its role in determining the redox state of the cells and their responses to free radicals, mitochondrial p66Shc protein has been regarded as part of a putative transduction pathway relevant to endothelial integrity. Future efforts should translate our knowledge of the mechanisms of aging and its interaction with risk factors into the development of new therapeutic strategies to prevent age-associated cardiovascular disease
Dysglycaemia, cardiovascular outcome and treatment. Is the jury still out?
No full text[No abstract available
- …
