Bone-marrow-derived mesenchymal stem cells (BM-MSCs) were found to markedly increase atherosclerotic lesion size. The aim of this paper was to investigate whether BM-MSCs contribute to vascular remodeling and calcification after balloon injury in hyperlipidemic rats. Labeled BM-MSCs were found in the lesion of hyperlipidemic rats after balloon injury. Comparing injury group, transferred BM-MSCs significantly triggered vascular negative remodeling, characterized by the changes of remodeling index (0.628 ± 0.0293 versus 0.544 ± 0.0217), neointimal area (0.078 ± 0.015 mm2 versus 0.098 ± 0.019 mm2), PCNA index (23.91 ± 6.59% versus 43.11 ± 5.31%), and percentage of stenosis (18.20 ± 1.09% versus 30.58 ± 1.21%). Apparent vascular calcification was detected in medial layers at 6 weeks after balloon angioplasty, which may be associated with upregulation of bone morphogenetic protein-2 (BMP-2). Our data indicated that unselected BM-MSCs transfer may induce vascular remodeling and calcification after balloon injury in hyperlipidemic rats.

Mitochondrial aldehyde dehydrogenase-2 (ALDH2) has been characterized as an important mediator of endogenous cytoprotection in the heart. This study was designed to examine the role of ALDH2 knockout (KO) in the regulation of cardiac function after endoplasmic reticulum (ER) stress. Wild-type (WT) and ALDH2 KO mice were subjected to a tunicamycin challenge, and the echocardiographic property was examined. Protein levels of six items-78 kDa glucose-regulated protein (GRP78), phosphorylation of eukaryotic initiation factor 2 subunit α (p-eIF2α), CCAAT/enhancer-binding protein homologous protein (CHOP), phosphorylation of Akt, p47 phox nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and 4-hydroxynonenal-were determined by using Western blot analysis. Cytotoxicity and apoptosis were estimated using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay and caspase-3 activity, respectively. ALDH2 deficiency exacerbated cardiac contractile dysfunction and promoted ER stress after ER stress induction, manifested by the changes of ejection fraction and fractional shortening. In vitro study revealed that tunicamycin significantly upregulated the levels of GRP78, p-eIF2α, CHOP, p47 phox NADPH oxidase and 4-hydroxynonenal, which was exacerbated by ALDH2 knockdown and abolished by ALDH2 overexpression, respectively. Overexpression of ALDH2 abrogated tunicamycin-induced dephosphorylation Akt. Inhibition of phosphatidylinositol 3-kinase using LY294002 did not affect ALDH2-conferred protection against ER stress, although LY294002 reversed the antiapoptotic action of ALDH2 associated with p47 phox NADPH oxidase. These results suggest a pivotal role of ALDH2 in the regulation of ER stress and ER stress-induced apoptosis. The protective role of ALDH2 against ER stress-induced cell death was probably mediated by Akt via a p47 phox NADPH oxidase-dependent manner. These findings indicate the critical role of ALDH2 in the pathogenesis of ER stress in heart disease.

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Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation and cardiac fibrosis. Emerging evidence indicated that endothelial-to-mesenchymal transition (Endo-MT) is a crucial event during organ fibrosis. This study was performed to clarify whether Endo-MT contributed to the progression of cardiac fibrosis in DCM. Cardiac samples from patients with DCM and control were obtained. The presence of endothelial markers, cluster of differentiation (CD)31 and vascular endothelial (VE)-cadherin, and mesenchymal markers, α smooth muscle actin (SMA) and fibroblast-specific protein 1 (FSP1) was performed using immunohistochemistry. Co-localization of endothelial markers and mesenchymal markers were identified using confocal immunofluorescence staining. Serum procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III amino-terminal propeptide (PIIINP) were measured by ELISA. Protein levels of Wnt, β-catenin and Snail were determined using western blot analysis. Immunohistochemistry and double-immunofluorescence staining demonstrated that the expression of CD31 and VE-cadherin were significantly decreased in DCM samples, whereas the FSP-1, and αSMA were significantly increased. CD31 and VE-cadherin labeling indexes were respectively negatively correlated with left ventricular end-diastolic diameter (LVEDD) (CD31 r=−0.82, P<0.01; VE-cadherin r=−0.73, P<0.01), while FSP-1 and αSMA were positively associated with LVEDD (αSMA r=0.65, P<0.01, FSP1 r=0.53, P<0.01) and left ventricular ejection fraction (αSMA r=−0.18, P<0.05; FSP1 r=−0.21, P<0.05). Furthermore, PICP and PIIINP levels were positively associated with the co-expression labeling indexes (CD31/SMA co-labeling index and PICP r=0.727, P<0.01; CD31/SMA co-labeling index and PIIINP r=0.741, P<0.01; VE-Cadherin/FSP-1 co-labeling index and PICP r=0.716, P<0.01; VE-cadherin/FSP-1 co-labeling index and PIIINP r=0.648, P<0.05). Western blot analysis indicated that proteins levels of Wnt signaling and snail were significantly increased in DCM samples. These results suggested that Endo-MT is potentially implicated in the pathogenesis of myocardial fibrosis and remodeling during the development of DCM, indicating a potential therapeutic target for DCM treatment.

Background: Whether the role of plasma heat shock protein 70 (HSP70) in acute myocardial infarction (AMI) is protective or detrimental remains debated, and the relationship between HSP70 and total occlusion remains elusive.Methods: A total of 112 patients with primary diagnosis of AMI and 52 patients with chronic coronary syndrome (CCS) were enrolled into the study. Plasma HSP70 level was determined by ELISA on day 1 and day 7 after the onset of AMI and was examined before angiography in patients with CCS. Peak NT-proBNP, high-sensitivity C-reactive protein (CRP), troponin T (cTnT), and left ventricular ejection fraction were measured.Results: Plasma HSP70 was significantly higher in CCS than AMI (P &lt; 0.0001), and it showed a significant decrease from day 1 to day 7 after AMI (P &lt; 0.01). Elevated HSP70 was associated with decreased levels of LDL-C (P &lt; 0.05), peak cTnT (R = −0.3578, P &lt; 0.0001), peak NT-proBNP (R = −0.3583, P &lt; 0.0001), and peak CRP (R = −0.3539, P &lt; 0.0001) and a lower diagnosis of AMI (R = −0.4016, P &lt; 0.0001) and STEMI (R = −0.3675, P &lt; 0.0001), but a higher diagnosis of total occlusion in target vessels (R = 0.1702, P &lt; 0.05). HSP70 may provide certain predictive value for the diagnosis of AMI, STEMI, and total occlusion in target vessels, and the area under the receiver operating characteristic curves were 0.7660, 0.7152, and 0.5984, respectively. HSP70 was also negatively associated with in-hospital stay (P &lt; 0.001) and positively correlated with left ventricular ejection fraction (LVEF) at 1-year follow-up (P &lt; 0.05), despite no association with in-hospital major adverse cardiovascular events (MACE).Conclusion: Plasma HSP70 level was found to decrease from day 1 to day 7 post-AMI, but the overall level of patients with AMI was lower than that of patients with CCS. However, the ability of HSP70 to identify clinically significant AMI and STEMI was moderate, and the predictive value to total occlusion was slight.

These data suggest the beneficial effect of olmesartan on cardiac structure and diastolic dysfunction, and it may be mediated through calcineurin pathway. This indicates a new therapeutic target for diastolic dysfunction.

Background: Endothelial-to-mesenchymal transition (Endo-MT) is associated with myocardial fibrosis in dilated cardiomyopathy (DCM). Endothelial-to-mesenchymal transition (Endo-MT) is induced by coxsackievirus B3 (CVB3) in cardiac microvascular endothelial cells (CMVECs). Bone morphogenetic protein 7 (BMP7) significantly inhibits Endo-MT and the progression of cardiac fibrosis. The study was aimed to investigate the effect and the underlying mechanism of BMP7 on Endo-MT in myocardial fibrosis induce by CVB3 infection in vivo. Methods: BALB/c mice were intraperitoneally injected by CVB3 to induce viral myocarditis (VMC). Mice were treated with BMP7 after CVB3 infection. Subsequently, all groups of mice were determined by echocardiography, histopathologic and molecular detection. Results: We found that the ratio of BMP7/TGF-β1 in mRNA levels was decreased obviously at different time points after CVB3 injection. BMP7 facilitated the recovery of cardiac function after CVB3 infection via inhibition of myocardial damage, collagen deposition. Double immunofluorescence staining indicated that Endo-MT was implicated in CVB3-induced myocardial fibrosis, which was attenuated by BMP7. The protein levels of pSmad3 and Smad4 were significantly upregulated in VMC group, as well as Wnt/β-catenin and the transcription factor snail. BMP7 treatment reversed the changes of these protein levels. Moreover, CO-IP demonstrated the crosstalk between β-catenin and Smad3 in VMC mice, which was downregulated by BMP7 treatment. Conclusions: These results indicated that BMP7 obviously ameliorated myocardial fibrosis in CVB3-infected mice via Endo-MT, which was involved in the TGF-β/Smad and Wnt/β-catenin pathway. β-Catenin/Smad3 interaction may be associated with Endo-MT in the development of viral myocardial fibrosis.

Background Guide extension catheters (GEC) are widely applied to cope with insufficient backup support in complex percutaneous coronary intervention (PCI). In the study, we aim to evaluate the feasibility and safety with a novel 5-4F tapered GEC used in complex lesion. Methods The single-center retrospective study enrolled a total of 615 patients, in whom the 5F or 5-4F Expressman GEC was used to facilitate PCI procedure. Demographic and procedural data were collected. Results 5F GEC was used in 295 patients and 5-4F tapered GEC in 320 patients. The average age was 63.6 ± 11.0 years and 81.6% of the patients were male. Severe calcification and chronic total occlusion (CTO) were the commonest indication for the GEC use. The 5-4F tapered GEC was frequently used in active greeting technique (AGT) during CTO intervention procedure than 5F GEC (6.1% vs. 13.1%, p < 0.001). The average depth of intubation was 41.5 ± 19.6 mm for the 5-4F tapered GEC and 24.4 ± 15.1 mm for 5F GEC (p < 0.001). The rate of successful device delivery with 5-4F GEC was higher than 5F GEC (95.6% vs. 98.4%, p = 0.037). Pressure damping with 5F GEC occurred frequently than 5-4F GEC (7.4% vs. 2.5%, p < 0.05). Similarly, the incidence of intraoperative hypotension was higher in 5F GEC than 5-4F GEC (4.7% vs.1.9%, p < 0.05). Conclusions The novel 5-4F tapered GEC was superior to the 5F GEC in facilitating successful completion of PCI in the majority of patients with complex lesions via transradial approach.