Inflammation is a condition that underscores many cardiovascular pathologies including endothelial dysfunction, but no link is yet established between the vascular pathology of the metabolic syndrome with a particular inflammatory cytokine. We hypothesized that impairments in coronary endothelial function in the obese condition the prediabetic metabolic syndrome is caused by TNF-α overexpression. To test this, we measured endothelium-dependent (acetylcholine) and -independent vasodilation (sodium nitroprusside) of isolated, pressurized coronary small arteries from lean control and Zucker obese fatty (ZOF, a model of prediabetic metabolic syndrome) rats. In ZOF rats, dilation to ACh was blunted compared with lean rats, but sodium nitroprusside–induced dilation was comparable. Superoxide (O ₂ · ⁻ ) generation was elevated in vessels from ZOF rats compared with lean rats, and administration of the O ₂ · ⁻ scavenger TEMPOL, NAD(P)H oxidase inhibitor (apocynin), or anti–TNF-α restored endothelium-dependent dilation in the ZOF rats. Real-time PCR and Western blotting revealed that mRNA and protein of TNF-α were higher in ZOF rats than that in lean rats, whereas eNOS protein levels were reduced in the ZOF versus lean rats. Immunostaining showed that TNF-α in ZOF rat heart is localized in endothelial cells and vascular smooth muscle cells. Expression of NAD(P)H subunits p22 and p40-phox were elevated in ZOF compared with lean animals. Administration of TNF-α more than 3 days also induced expression of these NAD(P)H subunits and abrogated endothelium-dependent dilation. In conclusion, the results demonstrate the endothelial dysfunction occurring in the metabolic syndrome is the result of effects of the inflammatory cytokine TNF-α and subsequent production of O ₂ · ⁻ .

Aims Right ventricle fractional area change (RVFAC), tissue Doppler and M-mode measurements of tricuspid systolic motion [tricuspid Sm and tricuspid annular plane systolic excursion (TAPSE)], and 3D echocardiography are the current non-invasive methods for the quantification of RV systolic function; RV deformation analysis by speckle-tracking echocardiography (STE) has recently allowed the analysis of RV performance. Using cardiac magnetic resonance (CMR) as the reference standard, this study aimed at exploring the correlation between the traditional (fractional shortening, s′RV, TAPSE) and innovative (strain) echocardiographic parameters and RV ejection fraction (RVEF) measured by CMR. Methods and results CMR and transthoracic echo-Doppler were performed in 63 patients referred for clinical assessment. Twenty-one presented the suspicion of myocarditis, 8 presented idiopathic dilated cardiomyopathy, 10 hypertrophic cardiomyopathy, 10 arrhythmogenic right ventricular dysplasia (ARVD), 5 infiltrative cardiomyopathy, and 9 other reasons. RVEF was measured by magnetic resonance imaging (MRI). RVFAC, tricuspid S′, and TAPSE were calculated in all patients. RV longitudinal strain (RVLS) by STE was assessed by averaging RV free-wall segments (free-wall RVLS) and by averaging all segments (global RVLS). The ROC analysis was applied for the assessment of diagnostic accuracy. Good correlations were found for TAPSE, tricuspid S′, and global RVLS with RVEF ( r = 0.45, r = 0.52, and r = −0.71, respectively; P = 0.01 for all). Close correlations between free-wall RVLS and RVFAC with RVEF were found ( r = −0.86 and r = 0.77, respectively; P < 0.0001 for both). Furthermore, free-wall RVLS demonstrated the highest diagnostic accuracy [area under curve (AUC) 0.92] and good sensitivity and specificity of 96 and 93%, respectively, to predict reduced RVEF <45%, using a cut-off value of less than −17.0%. Conclusion In a heterogeneous group of patients referred to CMR evaluation, conventional (TAPSE, FAC, and tricuspid S′) and novice (2D speckle-tracking-derived longitudinal strain) parameters of RV systolic function were compared and correlated with RVEF measured by MRI. All tested parameters were found to be independent predictors of reduced RVEF (<45%), but the strongest correlation was seen for the RV free-wall longitudinal strain.

Obesity is associated with marked increases in plasma leptin concentration, and hyperleptinemia is an independent risk factor for coronary artery disease. As a result, the purpose of this investigation was to test the following hypotheses: 1) leptin receptors are expressed in coronary endothelial cells; and 2) hyperleptinemia induces coronary endothelial dysfunction. RT-PCR analysis revealed that the leptin receptor gene is expressed in canine coronary arteries and human coronary endothelium. Furthermore, immunocytochemistry demonstrated that the long-form leptin receptor protein (ObRb) is present in human coronary endothelium. The functional effects of leptin were determined using pressurized coronary arterioles (<130 μm) isolated from Wistar rats, Zucker rats, and mongrel dogs. Leptin induced pharmacological vasodilation that was abolished by denudation and the nitric oxide synthase inhibitor N^ω-nitro-l-arginine methyl ester and was absent in obese Zucker rats. Intracoronary leptin dose-response experiments were conducted in anesthetized dogs. Normal and obese concentrations of leptin (0.1–3.0 μg/min ic) did not significantly change coronary blood flow or myocardial oxygen consumption; however, obese concentrations of leptin significantly attenuated the dilation to graded intracoronary doses of acetylcholine (0.3–30.0 μg/min). Additional experiments were performed in canine coronary rings, and relaxation to acetylcholine (6.25 nmol/l-6.25 μmol/l) was significantly attenuated by obese concentrations of leptin (625 pmol/l) but not by physiological concentrations of leptin (250 pmol/l). The major findings of this investigation were as follows: 1) the ObRb is present in coronary arteries and coupled to pharmacological, nitric oxide-dependent vasodilation; and 2) hyperleptinemia produces significant coronary endothelial dysfunction.