Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide. Despite the clinical long-term and near-term benefits of lowering cholesterol in, respectively, primary and secondary prevention of ASCVD, cholesterol levels remain under-treated, with many patients not achieving their recommended targets. The present article will review the latest updates on lipid management with emphases on the different classes of cholesterol-lowering agents and their clinical uses.

• MeSH
• anticholesteremika škodlivé účinky   terapeutické užití   MeSH
• ateroskleróza krev   diagnóza   farmakoterapie   mortalita   MeSH
• biologické markery krev   MeSH
• cholesterol krev   MeSH
• chování snižující riziko MeSH
• cvičení MeSH
• dyslipidemie krev   diagnóza   farmakoterapie   mortalita   MeSH
• lidé MeSH
• ochranné faktory MeSH
• rizikové faktory MeSH
• triglyceridy krev   MeSH
• výsledek terapie MeSH
• zdravá strava MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Obesity is a complex condition classically characterised by excessive body fat accumulation and represents one of the most important public health problems worldwide. Although several epidemiological studies have shown that elevated BMI is associated with higher morbidity, and with increased rate of death from all causes and from cardiovascular disease, accumulating evidence suggests that being overweight or obese may be protective (the so-called obesity paradox), at least in chronic diseases. These observations, not only question the validity of the BMI system, but also raise the intriguing question of whether we should redefine what the normal range of BMI is in individuals suffering from a chronic disease. In the present article, we review the available information on the association between elevated BMI and increased morbidity and mortality including obesity-related paradoxes, explore key aspects of the role and limitations of BMI as a measure of increased adiposity and outline potential solutions to address the current controversies regarding the impact of obesity on human health.

• MeSH
• analýza přežití MeSH
• index tělesné hmotnosti * MeSH
• lidé MeSH
• obezita diagnóza   MeSH
• rizikové faktory MeSH
• složení těla MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Modulation of Ca(2+) homoeostasis in cardiac myocytes plays a major role in beat-to-beat regulation of heart function. Previous studies suggest that sphingosine-1-phosphate (S1P), a biologically active sphingomyelin metabolite, regulates Ca(2+) handling in cardiac myocytes, but the underlying mechanism is unclear. In the present study, we tested the hypothesis that S1P-induced functional alteration of intracellular Ca(2+) handling includes the L-type calcium channel current (ICa,L) via a signalling pathway involving P21-activated kinase 1 (Pak1). Our results show that, in rat ventricular myocytes, S1P (100 nM) does not affect the basal activity of ICa,L but is able to partially reverse the effect of the β-adrenergic agonist Isoproterenol (ISO, 100 nM) on ICa,L. S1P (25 nM) also significantly prevents ISO (5 nM)-induced Ca(2+) waves and diastolic Ca(2+) release in these cells. Our further molecular characterisation demonstrates that Pak1 activity is increased in myocytes treated with S1P (25 nM) compared with those myocytes without treatment of S1P. By immunoprecipitation we demonstrate that Pak1 and protein phosphatase 2A (PP2A) are associated in ventricular tissue indicating their functional interaction. Thus the results indicate that S1P attenuates β-adrenergic stress-induced alteration of intracellular Ca(2+) release and L-type Ca(2+) channel current at least in part via Pak1-PP2A-mediated signalling.

• MeSH
• intracelulární signální peptidy a proteiny metabolismus   MeSH
• kardiomyocyty metabolismus   MeSH
• krysa rodu rattus MeSH
• lysofosfolipidy farmakologie   MeSH
• proteinfosfatasa 2 metabolismus   MeSH
• sfingosin analogy a deriváty   farmakologie   MeSH
• srdeční komory metabolismus   MeSH
• vápník metabolismus   MeSH
• vápníková signalizace účinky léků   MeSH
• vápníkové kanály - typ L metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH