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Cardiomyopathy is the leading cause of increased mortality in diabetes. In the present study, we investigated the effects of decorin (DCN) gene therapy on left ventricular function, cardiac inflammation and fibrosis in type 2 diabetes. Type 2 diabetes was induced in male Wistar rats by high fat diet (HFD, 60% of calories as fat) and STZ (20 mg/kg, intraperitoneal). Diabetic rats were divided into (n=6 for each group) the control group, the GFP-treated group and the DCN-treated group, received intravenous injection of saline solution, recombinant adeno-associated viral (rAAV)-GFP, and rAAV-DCN, respectively. We evaluated cardiac inflammation, fibrosis, left ventricular function at 6 months after gene delivery. Results turned out that rAAV-DCN treatment attenuated diabetic cardiomyopathy with improved LV function compared with control animals, which might be related to the reduced cardiac inflammation and fibrosis. These protective effects were associated with TGFβ1 pathway (ERK1/2 and smad-2) and NF-κB pathway, which may due to the decreased activation level of IGF-IR, increased expression of PKC-α and Hsp70. In conclusion, our results show that rAAV-mediated DCN therapy may be beneficial in the treatment of Diabetic Cardiomyopathy.

Fulminant myocarditis is primarily caused by infection with any number of a variety of viruses. It arises quickly, progresses rapidly, and may lead to severe heart failure or circulatory failure presenting as rapid-onset hypotension and cardiogenic shock, with mortality rates as high as 50%–70%. Most importantly, there are no treatment options, guidelines or an expert consensus statement. Here, we provide the first expert consensus, the Chinese Society of Cardiology Expert Consensus Statement on the Diagnosis and Treatment of Fulminant Myocarditis, based on data from our recent clinical trial (NCT03268642). In this statement, we describe the clinical features and diagnostic criteria of fulminant myocarditis, and importantly, for the first time, we describe a new treatment regimen termed life support-based comprehensive treatment regimen. The core content of this treatment regimen includes (i) mechanical life support (applications of mechanical respirators and circulatory support systems, including intraaortic balloon pump and extracorporeal membrane oxygenation), (ii) immunological modulation by using sufficient doses of glucocorticoid, immunoglobulin and (iii) antiviral reagents using neuraminidase inhibitor. The proper application of this treatment regimen may and has helped to save the lives of many patients with fulminant myocarditis.

Congenital coronary artery fistula (CAF) with huge coronary artery aneurysm is a very rare condition. In this paper, we describe a 26-year-old asymptomatic male patient with right coronary artery (RCA) to the left ventricle fistula with a huge coronary artery aneurysm which was diagnosed by multidetector computed tomography and coronary angiography. The patient received surgical treatment for coronary artery after diagnosis. Both RCA and a giant aneurysm were excised; surgical closure of CAF and coronary artery bypass grafting were performed on this patient. Two months after surgery, the enlarged left ventricle returned to normal as evaluated by echocardiography.

Fibrosis is the response of heart and other organs to injuries. Excessive fibrosis can cause organ dysfunction or even failure. Transforming-growth factor (TGF)-beta is a cytokine that induces fibroblast proliferation and increases the synthesis of a number of extracellular matrix proteins including collagens. Decorin (DCN) is a natural antagonist of TGF-beta. In the current study, we investigated the potential antifibrotic effects of DCN gene delivery by a recombinant adeno-associated viral (rAAV) vector to inhibit cardiac fibrosis in old, spontaneously hypertensive rats (SHRs), which develop severe cardiac and kidney fibrosis if without intervention. The rAAV-DCN vector was injected (at a dose of 1 x 10(11) vector genomes) via the tail vein into 5-month-old male SHRs, resulting in persistent, stable expression of DCN (up to 16 weeks). rAAV-DCN treatment significantly reduced collagen content and fibrosis in the heart and attenuated cardiomyocyte hypertrophy. Hemodynamics data at 16 weeks showed that DCN gene delivery induced a significant increase in left ventricular end-systolic pressure and maximal-minimal rate of pressure increase (+/-dp/dt(max)), but a decrease in left ventricular end-diastolic pressure (p0.05), compared with those of control animals. The expression of TGF-beta and alpha-smooth muscle actin, and the phosphorylation levels of Smad2 and p38 MAPK, were markedly reduced by rAAV-DCN treatment as compared with the controls. Thus, these results suggest that rAAV-mediated DCN overexpression led to the inhibition of hypertension-induced cardiac fibrosis and hypertrophy and improved cardiac function, and therefore may have therapeutic potential for organ fibrosis.

The inflammatory marker C-reactive protein (CRP) has been strongly correlated with the risk of cardiovascular disease. Some single-nucleotide polymorphisms (SNPs) have been reported to be associated with serum CRP levels. In this study, we assessed the genetic association between SNPs within the CRP gene and ischemic and hemorrhagic stroke in the Han Chinese population. This study comprises 564 ischemic stroke patients, 220 hemorrhagic stroke patients and 564 controls from the ethnic Han Chinese population in Wuhan. Four CRP SNPs, −757A>G (rs3093059), −717A>G (rs2794521), −286C>T>A (rs3091244) and +2147C>T (rs1205), were genotyped from patients using TaqMan assays. The A allele frequency for the −717A>G polymorphism was significant higher in controls than in ischemic stroke patients (P=0.037), after adjustment for traditional risk factors (odds ratio 0.28; 95% CI 0.12–0.65; P=0.003), suggesting a protective effect for this allele against ischemic stroke. Haplotype analysis showed that the H3 (G-C-C) haplotype conferred a significantly increased risk of ischemic stroke (odds ratio 1.052, 95% CI 1.001–1.106: P=0.047). Neither CRP genotypes nor haplotypes showed an association with hemorrhagic stroke. However, the frequency for haplotype H5 (A-T-C) was significantly higher in ischemic stroke than hemorrhagic stroke patients (P=0.0003). These data suggest that the CRP gene −717A allele confers a protective effect against ischemic stroke. Furthermore, the H3 haplotype (G-C-C) is an independent risk marker for ischemic stroke, whereas the H5 haplotype (A-T-C) can be used as a prognostic marker of hemorrhagic stroke.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by recurrent coma, ventricular tachycardias and the replacement of the myocardium with fatty and fibrous tissue. We described a 42-year-old female patient without clinical arrhythmias which was diagnosed as ARVC by magnetic resonance imaging (MRI), but the transvenous endomyocardial biopsy was not specific. The patient received heart transplantation due to her refractory heart failure and the pathology of explanted heart demonstrated typical replacement of fatty and fibrous tissue and piles of infiltrated lymphocytes in myocardial tissue. It is concluded that ARVC might not have any arrhythmias and inflammatory process may be involved in the mechanism of ARVC. Virtual slides The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/6573514507145351