期刊
HEART FAILURE REVIEWS
卷 8, 期 1, 页码 23-28出版社
SPRINGER
DOI: 10.1023/A:1022138803293
关键词
MMP; TIMP; PPAR; collagen; redox stress; eNOS; ADMA; DDAH
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL071010] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R29GM048595] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL-71010] Funding Source: Medline
- NIGMS NIH HHS [GM-48595] Funding Source: Medline
Accumulation of oxidized-matrix between the endothelium and myocytes is associated with endocardial endothelial (EE) dysfunction in diabetes and heart failure. High levels of circulating homocysteine (Hcy) have been demonstrated in diabetes mellitus (DM). These high levels of Hcy (hyperhomocysteinemia, HHcy) have a negative correlation with peroxisome proliferator activated receptor (PPAR) expression. Studies have demonstrated that Hey decreases bioavailability of endothelial nitric oxide (eNO), generates nitrotyrosine, and activates latent matrix metalloproteinase (MMP), instigating EE dysfunction. PPAR ligands ameliorate endothelial dysfunction and DM. In addition Hey competes with PPAR ligands. The understanding of molecular, cellular, and extracellular mechanisms by which Hcy amplifies DM will have therapeutic ramifications for diabetic cardiomyopathy.
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