心力衰竭的病理生学机制及治疗进展.ppt.ppt

* Hironaka E, Hongo M, Azegami M, Yanagisawa S, Owa M, Hayama M. Effects of angiotensin-converting enzyme inhibition on changes in left ventricular myocardial creatine kinase system after myocardial infarction: their relation to ventricular remodeling and function. Japanese Heart Journal. Vol. 44 (2003) , No. 4 pp.537-546 Naumann A, Neubauer S, Kuhlencordt P, Hu K, Tian R, Gaudron P, Ertl G. Myocardial contractile efficiency increases in proportion to a fetal enzyme shift in chronically infarcted rat hearts. Basic Res Cardiol. 2005 Mar;100(2):171-8. Epub 2005 Feb 3. Ingwall JS. Energy metabolism in heart failure and remodelling. Cardiovasc Res. 2009 Feb 15;81(3):412-9. Epub 2008 Nov 5. * 2. 胞外Ca2+内流受阻：电压依赖性+受体依赖性+ Na+- Ca2+交换体：膜内电位为正时，Na+向外，Ca2+向内 PMCA Plasma membrane Ca2+ ATPase There are four isoforms of PMCA, called PMCA 1 through 4.[5] ATP2B1 - PMCA1 ATP2B2 - PMCA2 ATP2B3 - PMCA3 ATP2B4 - PMCA4 Each isoform is coded by a different gene and is expressed in different areas of the body.[5] Alternate splicing of the mRNA transcripts of these genes results in different subtypes of these isoforms.[2] Over 20 splice variants have been identified so far.[2] Three PMCA isoforms, PMCA1, PMCA2, and PMCA3, occur in the brain in varying distributions.[6] PMCA1 is ubiquitous throughout all tissues in humans, and without it embryos do not survive.[4] Lack of PMCA4, which is also very common in many tissues, is survivable, but leads to infertility in males.[4] PMCA types 2 and 3 are activated more quickly and are, therefore, better suited to excitable cell types such as those in nervous and muscle tissue, which experiences large influxes of Ca2+ when excited.[5] PMCA types 1, 2, and 4 have been found in glial cells called astrocytes in mammals, though it was previously thought that only the NCX was present in glia.[8] Astrocytes help to maintain ionic balance in the extracellular space in the brain. Knock-out of PMCA2 causes inner ear problems, including hearing loss and