Statins inhibit the activation of Rho signaling, which negatively influences eNOS mRNA stability and activity, leading to an increased NO bioavailability

<p><b>Copyright information:</b></p><p>Taken from "The role of HMG-CoA reductase inhibition in endothelial dysfunction and inflammation"</p><p></p><p> 2007;3(5):567-577.</p><p>Published online Jan 2007</p><p>PMCID:PMC2291301.</p><p></p

Effect of cigarette smoke on monocyte procoagulant activity: Focus on platelet-derived brain-derived neurotrophic factor (BDNF)

<p>Cigarette smoke (CS) activates platelets, promotes vascular dysfunction, and enhances Tissue Factor (TF) expression in blood monocytes favoring pro-thrombotic states. Brain-derived neurotrophic factor (BDNF), a member of the family of neurotrophins involved in survival, growth, and maturation of neurons, is released by activated platelets (APLTs) and plays a role in the cardiovascular system. The effect of CS on circulating levels of BDNF is controversial and the function of circulating BDNF in atherothrombosis is not fully understood. Here, we have shown that human platelets, treated with an aqueous extract of CS (CSE), released BDNF in a dose-dependent manner. In addition, incubation of human monocytes with BDNF or with the supernatant of platelets activated with CSE increased TF activity by a Tropomyosin receptor kinase B (TrkB)-dependent mechanism. Finally, comparing serum and plasma samples of 12 male never smokers (NS) and 29 male active smokers (AS) we observed a significant increase in microparticle-associated TF activity (MP-TF) as well as BDNF in AS, while in serum, BDNF behaved oppositely. Taken together these findings suggest that platelet-derived BDNF is involved in the regulation of TF activity and that CS plays a role in this pathway by favoring a pro-atherothrombotic state.</p

Ang II and NO functions interplay to influence vascular tone, through different effects on RhoA pathway

<p><b>Copyright information:</b></p><p>Taken from "The role of HMG-CoA reductase inhibition in endothelial dysfunction and inflammation"</p><p></p><p> 2007;3(5):567-577.</p><p>Published online Jan 2007</p><p>PMCID:PMC2291301.</p><p></p

Redox Proteomics Identification of Oxidatively Modified Myocardial Proteins in Human Heart Failure: Implications for Protein Function

<div><p>Increased oxidative stress in a failing heart may contribute to the pathogenesis of heart failure (HF). The aim of this study was to identify the oxidised proteins in the myocardium of HF patients and analyse the consequences of oxidation on protein function. The carbonylated proteins in left ventricular tissue from failing (n = 14) and non-failing human hearts (n = 13) were measured by immunoassay and identified by proteomics. HL-1 cardiomyocytes were incubated in the presence of stimuli relevant for HF in order to assess the generation of reactive oxygen species (ROS), the induction of protein carbonylation, and its consequences on protein function. The levels of carbonylated proteins were significantly higher in the HF patients than in the controls (p<0.01). We identified two proteins that mainly underwent carbonylation: M-type creatine kinase (M-CK), whose activity is impaired, and, to a lesser extent, α-cardiac actin. Exposure of cardiomyocytes to angiotensin II and norepinephrine led to ROS generation and M-CK carbonylation with loss of its enzymatic activity. Our findings indicate that protein carbonylation is increased in the myocardium during HF and that these oxidative changes may help to explain the decreased CK activity and consequent defects in energy metabolism observed in HF.</p> </div

CK activity in cardiomyocytes.

<p>(<b>A</b>) CK activity in cell lysate measured after pretreatment with NAC (N-acetyl-l-cysteine) for 1 h, and then with angiotensin II (AngII) or phenylephrine (PE) for 4 h in the absence or presence of NAC. (<b>B</b>) Oxidative modification of CK activity <i>in vitro</i>. Purified human M-CK (30 units/mL) was incubated for 1 h at 25°C with H₂O₂ (1 mmol/L) in 25 mmol/L Tris-HCl (pH 7.4) in the absence or presence of 100 units/mL of catalase before measurement of CK activity. *p<0.05 <i>vs</i> CK alone. (<b>C</b>) CK activity in cells lysate measured after pretreatment with different ROS inhibitors for 1 h, and then with phenylephrine (PE) for 4 h. *p<0.05 <i>vs c</i>ontrol; ^#p<0.05 <i>vs</i> PE-treated cells, ^§p<0.05 <i>vs</i> AngII-treated cells (n = 5).</p

Immunofluorescence analysis of carbonylated proteins in cardiomyocytes after treatment with angiotensin II (AngII) or phenylephrine (PE).

<p>The cells were stained with anti-DNP antibody and visualised by means of a secondary antibody conjugated with Alexa Fluor dye 488. Representative of three independent experiments.</p

Intracellular generation of ROS in cardiomyocytes exposed to various compounds.

<p>(<b>A</b>) Relative DCF fluorescence of ROS generation. (<b>B</b>) Percentage increase in ROS generation vs control cells after 5 min. *p<0.01 vs control cells; n = 5. PE, phenylephrine; ISO, isoprotenerol; NE, norepinephrine; AngII, angiotensin II; ET-1, endothelin-1, TNFα, tumor necrosis factor α.</p

ELISA-measured protein carbonyl levels in the myocardium of 14 HF patients and 13 controls.

<p>*p<0.01 <i>vs</i> controls.</p

Detection of protein carbonyls after immunoprecipitation of M-CK from cell lysate.

<p>HL-1 cells were treated with angiotensin II (AngII) or phenylephrine (PE) for 24 h, and the immunoprecipitates were immunoblotted with anti-DNP and anti-CK. Representative of three independent experiments.</p

Baseline characteristics of the study patients.

*<p>By Fisher exact test.</p>§<p>by Wilcoxon Rank Sum Test.</p><p>ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker; CABG = coronary artery bypass graft surgery; CKD = chronic kidney disease; CRP = C-reactive protein; eGFR = estimated glomerular filtration rate; NA = not applicable; PCI = percutaneous coronary intervention.</p