内源性含硫气体分子的心血管调节（英文）课件幻灯

Endogenous Sulfur-containing Gaseous Molecules BBRC 1997, 2004; J Infect 2004 H2S is endogenously produced in cardiovascular system 3 Modulates cardiac contractility Modulate proliferation and apoptosis of the vascular smooth muscle cells via MAPK pathway Relax blood vessels Relax pulmonary arteries Inhibits proliferation of the pulmonary arterial smooth muscle cells Pulmonary Circulation Systemic Circulation Cardiac Functions H2S 120 (5):389-393 H2S 128(5):3205-11 Endogenous H2S decreased at the acute stage of COPD N=77 17 inferior vena cava abdominal aorta A rat model of high pulmonary blood flow- induced pulmonary hypertension by an abdominal aorta-inferior vena cava shunting operation 18 marker D1 D3 W1 W4 W8 W11 Up-regulated at the early stage of high pulmonary blood flow- induced pulmonary hypertension Down-regulated at the late stage of high pulmonary blood flow-induced pulmonary hypertension u H2S/CSE pathway exhibited the following changes: Circ J, 2005 H2S 27 (3): 299306 In vascular calcification model, H2S/CSE pathway down-regulated 25 H2S 27 (3): 299306 control VDN VDN+L VDN+H 26 H2S and Cardiovascular Diseases Hypertension Hypoxic pulmonary hypertension Pulmonary blood flow-induced pulmonary hypertension Vascular calcification Hyperhomocysteinemia (HHcy) Endotoxic and septic shock Myocardial injury & coronary artery disease 27 H2S & HHcy Amino Acids (2008) 34:573585 H2S decreased plasma Hcy level and reversed HCY-induced myocardial injury in HHcy rats 28 Hcy-induced mitochondrial respiration inhibition Hcy-induced mitochandrial enzyme dysfunction (SDH, COX) Hcy-stimulated H2O2 and superoxide anion production Hcy-induced antioxidase inhibition (Mn-SOD) Hcy-induced endoplasmic reticulum stress HHcy H2S inhibit reverse inhibit reverse reverse Mechanism by which H2S antagonized Hcy-induced cardiovascular injury Amino Acids (2008) 34:573585 SDH: succinic dehydrogenase COX: cytochrome oxidase Mn-SOD: manganese-superoxide dismutase H2S & HHcy 29 H2S and Cardiovascular Diseases Hypertension Hypoxic pulmonary hypertension Pulmonary blood flow-induced pulmonary hypertension Vascular calcification Hyperhomocysteinemia (HHcy) Endotoxic and septic shock Myocardial injury & coronary artery disease 30 H2S & shock J Infection, 2003, 47:155-160 In endotoxic and septic shock, the increased H2S production was involved in its pathogenesis 31 H2S and Cardiovascular Diseases Hypertension Hypoxic pulmonary hypertension Pulmonary blood flow-induced pulmonary hypertension Vascular calcification Hyperhomocysteinemia (HHcy) Endotoxic and septic shock Myocardial injury & coronary artery disease 32 Endogenous H2S production was reduced in ISO-induced myocardial injury H2S & Myocardial injury 1Plasma H2S level 2H2S production in the heart 3CSEmRNA expression Biochem Biophys Res Co, 318 (2004) 756763 33 H2S protects the structure and the contractility of the myocardium The mechanism is associated with the getting rid of free radicals H2S & Myocardial injury Biochem Biophys Res Co, 318 (2004) 756763 34 Endogenous H2S production was inhibited in cardiomyopathy induced by adriamycin (ADR) Plasma H2S levelH2S content in rat heart H2S & Myocardial injury 35 NaHS-treatment improved ADR-induced depression of cardiac functions ADR+NaHS-L ADR+NaHS-H H2S & Myocardial injury 36 NaHS-treatment lessened ADR-induced myocardial damage controlADR ADR+H2S-LADR+H2S-H controlADR ADR+NaHS-LADR+NaHS-H H2S & Myocardial injury 37 GroupPlasma MDA (nmol/L) Myocardial MDA (nmol/g) Myocardial SOD activity (U/mg) Myocardial GPx activity (U/mg) Control 3.970.554.340.64139.1511.9238.669.18 ADR5.291.06 aa6.270.94 aa105.0726.95 aa25.578.98 aa ADR +NaHS4.720.735.080.99 bb c116.0215.7635.016.6 b c NaHS-treatment inhibited ADR-induced oxidative stress by increasing antioxidase activity NaHS:14umol/kg Decreased production of H2S is involved in the pathogenesis of ADR-induced cardiomyopathy through inhibiting oxidative stress H2S & Myocardial injury 38 H2S & CAD Clinical Research Decreased plasma H2S level correlate with the severity of CAD and coronary artery lesions SAP: Stable angina patients UAP: Unstable angina patients AMI: Acute myocardial infarction 39 There are other interesting studies on the role of H2S in the pathogenesis of cardiovascular diseases Vascular neointima formation Myocardial infarction Haemorragic shock H2S preconditioning for myocardial injury H2S postconditioning for myocardial injury Angiogenesis Left-ventricular remodeling in SHR Others FDU FDU US CA Sg Z-Sg Sg CH 40 Conclusion u H2S is important for the homeostatic control of cardiovascular functions u Abnormal metabolism and function of H2S contribute to the development of cardiovascular disease u Correction of these abnormalities in the H2S/CSE would be beneficial for the prognosis of cardiovascular disease 41 Perspective u Clarify the significance of H2S as a gasotransmitter u Provide insight into the mechanisms of many H2S abnormality-related diseases u Seek for the way of preventive and therapeutic strategies based on the biological effects of H2S 42 We demonstrated: SO2 could be endogenously generated in vascular tissues SO2 could relax aortic rings, at least in part, through an L-type calcium channel, suggesting that it might act as a vasoactive mol