The peroxisome proliferator-activated receptors (PPAR) belong to the nuclear superfamily of ligand-activated transcription factors. PPARgamma acts as a nutrient sensor that regulates several homeostatic functions. Its disruption can lead to vascular pathologies, disorders of fatty acid/lipid metabolism and insulin resistance. PPARgamma can modulate several signaling pathways connected with blood pressure regulation. Firstly, it affects the insulin signaling pathway and endothelial dysfunction by modulation of expression and/or phosphorylation of signaling molecules through the PI3K/Akt/eNOS or MAPK/ET-1 pathways. Secondly, it can modulate gene expression of the renin- angiotensin system - cascade proteins, which potentially slow down the progression of atherosclerosis and hypertension. Thirdly, it can modulate oxidative stress response either directly through PPAR or indirectly through Nrf2 activation. In this context, activation and functioning of PPARgamma is very important in the regulation of several disorders such as diabetes mellitus, hypertension and/or metabolic syndrome.

• MeSH
• buněčný převod mechanických signálů MeSH
• hypertenze patofyziologie   MeSH
• inzulin metabolismus   MeSH
• krevní tlak * MeSH
• lidé MeSH
• modely kardiovaskulární MeSH
• oxid dusnatý metabolismus   MeSH
• oxidační stres MeSH
• PPAR gama metabolismus   MeSH
• renin-angiotensin systém * MeSH
• signální transdukce MeSH
• vazodilatace MeSH
• vazokonstrikce MeSH
• vazomotorický systém patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Mechanisms underlying atrial fibrillation (AF), the most common cardiac arrhythmia, particularly in aged population, are not fully elucidated. We have previously shown an increased propensity of old guinea pigs (GPs) heart to inducible AF when comparing to young animals. This study aimed to verify our hypothesis that susceptibility of aged heart to AF may be attributed to abnormalities in myocardial connexin-43 (Cx43) and extracellular matrix that affect cardiac electrical properties. Experiments were conducted on male and female 4-week-old and 24-week-old GPs. Atrial tissue was processed for analysis of Cx43 topology using immunohistochemistry, expression of Cx43 protein using immunobloting, and expression of mRNA of Cx43 and extracellular matrix metalloproteinase-2 (MMP-2) using real time PCR. Immunohistochemistry revealed uniform Cx43 distribution predominantly on lateral sides of the cardiomyocytes of young male and female GP atria. In contrast, non-uniform distribution, mislocalization and reduced immunolabeling of Cx43 were detected in atria of old GPs. In parallel, the atrial tissue levels of Cx43 mRNA were significantly decreased, while mRNA expression of MMP-2 was significantly increased in old versus young GPs. The changes were more pronounced in old GPs males comparing to females. Findings indicate that age-related down-regulation of atrial Cx43 and up-regulation of MMP-2 as well as disordered Cx43 distribution can facilitate development of AF in old guinea pig hearts.

• MeSH
• down regulace MeSH
• fibrilace síní etiologie   metabolismus   MeSH
• konexin 43 metabolismus   MeSH
• matrixová metaloproteinasa 2 metabolismus   MeSH
• morčata MeSH
• myokard metabolismus   ultrastruktura   MeSH
• stárnutí metabolismus   MeSH
• upregulace MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH