Cardiomyopathy often leads to dilated cardiomyopathy (DCM) when caused by viral myocarditis. Apoptosis is long considered as the principal process of cell death in cardiomyocytes, but programmed necrosis or necroptosis is recently believed to play an important role in cardiomyocyte cell death. We investigated the role of necroptosis and its interdependency with other processes of cell death, autophagy, and apoptosis in a rat system of experimental autoimmune myocarditis (EAM). We successfully created a rat model system of EAM by injecting porcine cardiac myosin (PCM) and showed that in EAM, all three forms of cell death increase considerably, resulting in the deterioration of cardiac conditions with an increase in inflammatory infiltration in cardiomyocytes. To explore whether necroptosis occurs in EAM rats independent of autophagy, we treated EAM rats with a RIP1/RIP3/MLKL kinase-mediated necroptosis inhibitor, Necrostatin-1 (Nec-1). In Nec-1 treated rats, cell death proceeds through apoptosis but has no significant effect on autophagy. In contrast, autophagy inhibitor 3-Methyl Adenine (3-MA) increases necroptosis, implying that blockage of autophagy must be compensated through necroptosis. Caspase 8 inhibitor zVAD-fmk blocks apoptosis but increases both necroptosis and autophagy. However, all necroptosis, apoptosis, and autophagy inhibitors independently reduce inflammatory infiltration in cardiomyocytes and improve cardiac conditions. Since apoptosis or autophagy is involved in many important cellular aspects, instead of suppressing these two major cell death processes, Nec1 can be developed as a potential therapeutic target for inflammatory myocarditis.

Fibrinogen-like protein 2 (Fgl2) is involved in apoptosis, angiogenesis and inflammatory response. Diabetes is closely associated with apoptosis, angiogenesis and coagulation. So it allowed us to assume that Fgl2 plays an important role during the process of diabetic cardiomyopathy (DCM). In the present study, we test that the feasibility of Fgl2 as a therapeutic target for the treatment of DCM and its possible molecular mechanism involved. We found that Fgl2 gene silencing inhibits apoptosis and improves heart function of streptozotocin (STZ)-induced diabetes rats, the possible mechanism maybe that Fgl2 gene silencing reduces the tumour necrosis factor (TNF)±levels, decreases the expression of B-cell lymphoma-2 (bcl2), bcl-2-associated X (bax), toll-like receptors 4 (TLR4) and p38 mitogen-activated protein kinase (MAPK). In conclusion, Fgl2 is a potent target to treat DCM.

Background: Lipoprotein(a) [Lp(a)] is associated with coronary atherosclerotic heart disease, aortic stenosis, stroke, and heart failure. We aimed to determine the relationship between Lp(a) and aortic dissection (AD).Methods: Two hundred patients with AD were included in our case group. The control group consisted of 200 non‐AD people who were age‐ (±5 years) and gender‐matched to the case group. Data were collected retrospectively, including hypertension, smoking, coronary artery disease, diabetes mellitus, Lp(a), total cholesterol, triglyceride, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol. The association between Lp(a) and AD was studied using univariate and multivariate logistic regression analysis.Results: Patients with AD had greater median Lp(a) concentrations than non‐AD people (152.50 vs. 81.75 mg/L). Lp(a) was associated with AD in a multivariate logistic regression analysis (odds ratio, 8.03; 95% confidence interval, 2.85–22.62), comparing those with Lp(a) quartile 4 with those with Lp(a) quartile 1. Stratified analysis showed that this relationship was observed in both men and women, as well as in older and younger individuals.Conclusions: High levels of Lp(a) are strongly associated with AD, independent of other cardiovascular risk factors.

Postembryonic angiogenesis is mainly induced by various proangiogenic factors derived from the original vascular network. Previous studies have shown that the role of Ang‐2 in angiogenesis is controversial. Tip cells play a vanguard role in angiogenesis and exhibit a transdifferentiated phenotype under the action of angiogenic factors. However, whether Ang‐2 promotes the transformation of endothelial cells to tip cells remains unknown. Our study found that miR‐221‐3p was highly expressed in HCMECs cultured for 4 h under hypoxic conditions (1% O₂). Moreover, miR‐221‐3p overexpression inhibited HCMECs proliferation and tube formation, which may play an important role in hypoxia‐induced angiogenesis. By target gene prediction, we further demonstrated that Ang‐2 was a downstream target of miR‐221‐3p and miR‐221‐3p overexpression inhibited Ang‐2 expression in HCMECs under hypoxic conditions. Subsequently, qRT‐PCR and western blotting methods were performed to analyse the role of miR‐221‐3p and Ang‐2 on the regulation of tip cell marker genes. MiR‐221‐3p overexpression inhibited CD34, IGF1R, IGF‐2 and VEGFR2 proteins expression while Ang‐2 overexpression induced CD34, IGF1R, IGF‐2 and VEGFR2 expression in HCMECs under hypoxic conditions. In addition, we further confirmed that Ang‐2 played a dominant role in miR‐221‐3p inhibitors promoting the transformation of HCMECs to tip cells by using Ang‐2 shRNA to interfere with miR‐221‐3p inhibitor‐treated HCMECs under hypoxic conditions. Finally, we found that miR‐221‐3p expression was significantly elevated in both serum and myocardial tissue of AMI rats. Hence, our data showed that miR‐221‐3p may inhibit angiogenesis after acute myocardial infarction by targeting Ang‐2 to inhibit the transformation of HCMECs to tip cells.