Diallyl trisulfide and diallyl disulfide ameliorate cardiac dysfunction by suppressing apoptotic and enhancing survival pathways in experimental diabetic rats.

Cardiovascular disease is one of the major causes of mortality in diabetic patients. Mounting studies have shown that garlic exhibits, possibly through its antioxidant potential, diverse biological activities. In this study, we investigated the alleviating effects of garlic oil (GO) and its two major components, diallyl disulfide (DADS) and diallyl trisulfide (DATS), on diabetic cardiomyopathy in rats. Physiological cardiac parameters were obtained using echocardiography. Apoptotic cells were evaluated using TUNEL and DAPI staining. Protein expression levels were determined using Western blotting analysis. Our findings indicated that in diabetic rat hearts significantly decreased fractional shortening percentage, increased levels of nitrotyrosine, an elevated number of TUNEL-positive cells, enhanced levels of caspase 3 expression, and decreased PI3K-Akt signaling pathway activities were observed. Furthermore, all of these alterations were reversed following both GO and DATS (or DADS) administrations through increasing PI3K-Akt signaling pathway activities and inhibiting both the death receptor-dependent and the mitochondria-dependent apoptotic pathways. In conclusion, this study shows that DATS and DADS, with the efficacy order DATS > DADS, have the therapeutic potential for ameliorating diabetic cardiomyopathy. Furthermore, the therapeutic effects of GO on diabetic cardiomyopathy should be mainly from DATS and DADS.

Primary adipose-derived stem cells enriched by growth factor treatment improves cell adaptability toward cardiovascular differentiation in a rodent model of acute myocardial infarction.

The heterogeneous cell population in primary adipose-derived adult stem cells (ADAS) and difficulty in keeping their primitive properties have posed certain limitations on using these cells for cell therapy. Therefore, our objective was to generate a population of cells enriched from the adipose stromal-vascular fraction (SVF) with greater differentiation potential than ADAS and to explore the mechanism behind the repair of the injured myocardium in vivo. The distinct population of adipose stromal cells was enriched by immediate treatment of the growth factor cocktail (EGF and PDGF-BB) to the freshly isolated SVF. These cells (ADAS-GFs) had distinct cell morphology from ADAS and in average had a smaller size. They presented co-expression of CD140a (pericytic markers) and CD34 (hematopoietic marker), more obvious mesenchymal (CD13, CD29, CD44, CD90 and CD117) markers, but rare KDR, and were negative for CD45 and CD31. ADAS-GFs not only spontaneously expressed endothelial cell markers and formed capillary-like tubes on Matrigel but also clearly expressed early cardiomyocyte marker genes when embedded in methylcellulose-based medium. In Sprague-Dawley (SD) rats with left anterior descending artery (LAD)-induced myocardial infarction (MI), the ADAS-GFs transplanted group had the left ventricular function significantly improved compared with the ADAS transplanted group or the control group at 12 weeks post transplantation. The immunofluorescence staining revealed that the transplanted ADAS-GFs expressed GATA4, betamyosin heavy chain and troponin T protein but not vWF. More capillaries were also observed around the infarcted zone in the ADAS-GFs transplanted group. These data suggested that ADAS-GFs with a higher proangiogenic potential may restore the cardiac function of infarcted myocardium via the direct cardiomyocyte differentiation as well as angiogenesis recruitment.

Lipopolysaccharide induces cellular hypertrophy through calcineurin/NFAT-3 signaling pathway in H9c2 myocardiac cells.

Evidences suggest that lipopolysaccharide (LPS) participates in the inflammatory response in the cardiovascular system; however, it is unknown if LPS is sufficient to cause the cardiac hypertrophy. In the present study, we treated H9c2 myocardiac cells with LPS to explore whether LPS causes cardiac hypertrophy, and to identify the precise molecular and cellular mechanisms behind hypertrophic responses. Here we show that LPS challenge induces pathological hypertrophic responses such as the increase in cell size, the reorganization of actin filaments, and the upregulation of hypertrophy markers including atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in H9c2 cells. LPS treatment significantly promotes the activation of GATA-4 and the nuclear translocation of NFAT-3, which act as transcription factors mediating the development of cardiac hypertrophy. After administration of inhibitors including U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), CsA (calcineurin inhibitor), FK506 (calcineurin inhibitor), and QNZ (NFkappaB inhibitor), LPS-induced hypertrophic characteristic features, such as increases in cell size, actin fibers, and levels of ANP and BNP, and the nuclear localization of NFAT-3 are markedly inhibited only by calcineurin inhibitors, CsA and FK506. Collectively, these results suggest that LPS leads to myocardiac hypertrophy through calcineurin/NFAT-3 signaling pathway in H9c2 cells. Our findings further provide a link between the LPS-induced inflammatory response and the calcineurin/NFAT-3 signaling pathway that mediates the development of cardiac hypertrophy.

Brachial loop: transradial technique to overcome this rare anatomic variation.

A brachial loop is a rare anatomic variation and can result in the failure of transradial coronary procedures. We report a brachial loop encountered in a patient undergoing a coronary angiogram. During this angiogram, a 0.035'' J-tipped Teflon-coated guidewire met with resistance in the brachial artery because of this rare vascular loop. In this case report, we discuss the technique we used to manage this rare condition. Interventional cardiologists should keep in mind that resistance of the guidewire can result in major vessel complications during the transradial approach.

Worsening of left ventricular ejection fraction induced by dipyridamole on Tl-201 gated myocardial perfusion imaging predicts significant coronary artery disease.

BACKGROUND: Vasodilator stress on myocardial perfusion imaging has been found to induce ischemic stunning, which may present as transient worsening of left ventricular ejection fraction (LVEF) or regional wall motion abnormality. This study aimed to evaluate the significance of stress-induced worsening of LVEF in the diagnosis of coronary artery disease (CAD) on dipyridamole thallium 201 gated single photon emission computed tomography (SPECT). METHODS AND RESULTS: The study included 126 patients who underwent dipyridamole Tl-201 gated SPECT and coronary angiography within 3 months. Poststress and 4-hour rest images were obtained, and LVEF was calculated by use of automated software (QGS 3.0). A decrease in LVEF of 6% or greater from rest to poststress was considered significant, and this threshold was determined by the serial reproducibility assessment of Tl-201 gated SPECT. If worsening of LVEF was used as the criterion for detecting significant CAD (> or = 70% coronary stenoses in > or = 1 vessel), the sensitivity, specificity, positive predictive value, and negative predictive value were 35%, 93%, 90%, and 44%, respectively. CONCLUSION: Dipyridamole-induced worsening of LVEF, as shown by Tl-201 gated SPECT, is a valuable nonperfusion marker of significant CAD. Although the sensitivity of LVEF worsening in detecting significant CAD is only 35%, the specificity is as high as 93%.

Relationship of transient ischemic dilation in dipyridamole myocardial perfusion imaging and stress-induced changes of functional parameters evaluated by Tl-201 gated SPECT.

BACKGROUND: This study assessed whether transient ischemic dilation (TID) of the left ventricle is related to ischemic stunning, manifested by stress-induced decrease of left ventricular ejection fraction (LVEF) and worsening of wall motion, by use of dipyridamole-stress and redistribution thallium 201 gated single photon emission computed tomography (SPECT). METHODS AND RESULTS: Ninety-two consecutive patients undergoing dipyridamole Tl-201 gated SPECT were included. Patients with a TID ratio in the highest quartile were defined as having TID. In patients with TID, end-diastolic volume (EDV) and end-systolic volume (ESV) were both significantly greater on dipyridamole-stress images than on redistribution images (P < .001). The degree of enlargement was much greater for ESV than EDV. In patients without TID, EDV and ESV were both decreased after stress (P < .001). Patients with TID had a lower mean LVEF on dipyridamole-stress images than on redistribution images (P < .001). Patients without TID had a higher mean LVEF on dipyridamole-stress images than on redistribution images (P < .001). Patients with TID had a significant worsening of global wall motion on dipyridamole-stress images than on redistribution images (P < .001), but patients without TID did not. CONCLUSION: TID was significantly correlated with ischemic stunning, and the enlargement of ESV was an important factor resulting in TID.