In the mouse model of dilated cardiomyopathy, endothelial dysfunction in coronary circulation is present in the late but not the early stage of heart failure pathology and is characterized by a decrease in NO bioavailability and a compensatory increase in PGI(2). Both the decrease in NO activity and the increase in PGI(2) activity may result from excessive O(2) (-) production by cardiac NADPH oxidase in Tgalphaq*44 hearts.

■ AbstractApolipoprotein M (apoM) is a 26-kDa protein expressed mainly in the liver and kidneys. It is present predominantly in high-density lipoproteins (HDL). ApoM expression is influenced by the hepatocyte nuclear factor-1α (HNF-1α), which is a transcription factor associated with the pathogenesis of MODY. Some earlier data suggested that apoM levels were lower in the serum of HNF-1α MODY subjects, than in that of other diabetics and healthy controls. The aim of this study was to evaluate apoM as a biomarker for HNF-1α MODY. We included in this study 48 HNF-1α mutation carriers (40 diabetic patients and 8 subjects with normal glucose levels in the fasted state) from the Polish Nationwide Registry of MODY. In addition, we examined 55 T2DM patients and 55 apparently healthy volunteers who had normal fasting glucose levels. ApoM was measured by the sandwich dot-blot technique with recombinant apoM (Abnova) as a protein standard, mouse anti-human apoM monoclonal primary antibody and rat anti-mouse HRPconjugated secondary antibody (BD Biosciences). Mean apoM level in the MODY group was 13.6 µg/ml, SD 1.9 (13.5 µg/ml, SD 1.7 in diabetic subjects and 13.9 µg/ml, SD 2.0 in non-diabetic mutation carriers respectively). In the T2DM group, mean apoM level was 13.7 µg/ml, SD 2.1, while it reached 13.8 µg/ml, SD 2.0 in healthy controls. There was no difference between apoM serum concentrations in all the study groups. In summary, our study showed no association between HNF-1α mutations resulting in MODY phenotype and apoM levels. Thus, we cannot confirm the clinical usefulness of apoM as a biomarker of HNF-1α MODY.Keywords: maturity onset diabetes of the young · MODY · apolipoprotein M · HNF-1alpha

Enhancement by atorvastatin of the ACE2/Ang-(1-7) axis in VSMCs could represent a new and beneficial mechanism on cardiovascular action of this widely used drug.

Nitric oxide plays a fundamental role in the regulation of blood flow. Here we analyzed compensatory mechanisms for the genetic eNOS deficiency in aorta and in coronary circulation. Vasodilation induced by acetylcholine, bradykinin, adenosine, and ADP as well as by S-nitroso-penicillamine (SNAP) was assessed in isolated aorta and in isolated mouse hearts from eNOS-/- and age-matched eNOS+/+ mice. In aorta from eNOS+/+ mice acetylcholine-induced vasodilation was entirely dependent on NO, and this response was absent in aorta from eNOS-/- mice. In eNOS+/+ mouse hearts responses induced by bradykinin, adenosine and ADP were partially dependent on NO, but not on PGI2, cytochrome P450-dependent metabolites, or H2O2. On the other hand, vasodilation induced by acetylcholine involved NO, but not PGI2, in its immediate, short-lasting phase, whereas PGI2 and NO mediated delayed, longer-lasting phase of this response. In eNOS-/- mouse hearts coronary vasodilator function was compensated. Responses induced by acetylcholine and adenosine, but not by bradykinin or ADP, were in part compensated by NO, most likely derived from nNOS. However, the major mechanisms compensating for the loss of eNOS in the coronary circulation did not rely on NO, PGI2, cytochrome P450-derived metabolites of arachidonic acid or on H2O2. Deficiency of eNOS is largely compensated in coronary circulation but not in aorta.

Atherosclerosis and nonalcoholic fatty liver disease (NAFLD) are frequent causes of death in the Western countries. Recently, it has been shown that autophagy dysfunction plays an important role in the pathogenesis of both atherosclerosis and NAFLD; thus, activators of autophagy might be useful for novel therapeutic interventions. Trehalose—a naturally occuring disaccharide present in plants, bacteria, fungi, insects, and certain types of shrimps—is a known inducer of autophagy. However, according to the literature, its anti-atherosclerotic and anti-steatotic potential seem to depend on the experimental setting. The aim of our study was to comprehensively describe the influence of a prolonged treatment with orally administered trehalose on the development of atherosclerotic lesions and hepatic steatosis in apolipoprotein E knockout (apoE−/−) mice in an experimental set up reflecting both moderate and severe proatherogenic conditions: male apoE−/− mice on a chow diet (CD) and female apoE−/− mice fed with a high-fat diet (HFD). We found that exogenous trehalose inhibited atherosclerosis and attenuated hepatic steatosis in apoE−/− mice. Such effects of trehalose were not associated with changes of plasma cholesterol, low-density lipoproteins (LDL), or high-density lipoproteins (HDL). Moreover, the anti-steatotic action of trehalose in the liver was associated with the induction of autophagy. The exact molecular mechanisms of both the anti-atherosclerotic action of trehalose and its inhibitory effect on liver steatosis require further clarification.