Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited cardiomyopathy, with an adult incidence rate of 1:500 to 1:200.^1,2 Up to 75% of patients with HCM have left ventricular outflow tract (LVOT) obstruction under resting conditions (defined as gradients ≥30 mm Hg) or with provocation (<30 mm Hg at rest and ≥30 mm Hg with physiologic provocation).¹ Dynamic LVOT hypertrophic obstructive cardiomyopathy (HOCM) is the key mechanism leading to clinical symptoms in patients and significantly increased mortality.³ Asymmetric myocardial hypertrophy with systolic anterior motion of the mitral valve is the pathophysiologic cause of LVOT obstruction.⁴ Although medical treatment with β-blockers, nondihydropyridine calcium channel blockers, and disopyramide have a class I indication in current guidelines,¹ they are effective in reducing LVOT obstruction in less than 50% of patients resulting in a large patient population with drug-refractory sypmtoms.⁵ Therefore, effective ventricular septal reduction with either surgical myectomy or alcohol septal ablation (ASA) is the main invasive treatment for LVOT obstruction. Unfortunately, the success of ASA is limited by septal coronary anatomy and alternative nonsurgical techniques have had limited success.^6,7

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM). However, the mechanisms underlying DCM-induced cardiac injury remain unclear. Recently, the role of cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) signaling and pyroptosis in DCM has been investigated. Based on our previous results, this study was designed to examine the impact of irisin, mitochondrial ubiquitin ligase (MITOL/MARCH5), and cGAS/STING signaling in DCM-induced cardiac dysfunction and the effect of gasdermin D (GSDMD)-dependent pyroptosis. High-fat diet-induced mice and H9c2 cells were used for cardiac geometry and function or pyroptosis-related biomarker assessment at the end of the experiments. Here, we show that DCM impairs cardiac function by increasing cardiac fibrosis and GSDMD-dependent pyroptosis, including the activation of MITOL and cGAS/STING signaling. Our results confirmed that the protective role of irisin and MITOL was partially offset by the activation of cGAS/STING signaling. We also demonstrated that GSDMD-dependent pyroptosis plays a pivotal role in the pathological process of DCM pathogenesis. Our results indicate that irisin treatment protects against DCM injury, mitochondrial homeostasis, and pyroptosis through MITOL upregulation.

Background: Bovine pericardium can be used for cardiovascular repair surgeries, but challenges involving biocompatibility and durability remain. This study aimed to carry out pre-clinical testing of aortic valve replacement using an aortic valve prosthesis made of bovine pericardium modified with glutaraldehyde (GA) and 2,3-butanediol (BD). Methods: The mechanical, plasma protein adsorption, platelet adhesion, collagenase digestion, and ninhydrin properties of the material (control vs. GA vs. GA + BD) were tested. All 3 tissues were implanted in rats and observed after 8 weeks under microscopy with alizarin red staining for calcification. Aortic valves made from the fully-treated material were implanted in sheep. A commercial bioprosthesis was used as control. Effectiveness and safety indicators were observed at 180 days after implantation. Results: Compared with the control group, the GA + BD material showed higher elongation at breaking and tensile load (both P<0.05), lower plasma protein adsorption, lower platelet adhesion, lower collagenase digestion, lower ninhydrin value, and higher cross-linking (all P<0.05). After implantation in rat models, the GA + BD material showed little or no dissolution; there was no obvious calcification; and it was surrounded by a small amount of fibrosis, with peripheral capillary proliferation. After implantation in sheep models, the aortic valve leaflets of the experimental animals freely opened and closed, their surface was smooth, and no abnormal echo was observed. The echocardiographic results and hemodynamic were comparable between the two groups. All safety parameters were normal. Conclusions: Modification of bovine pericardium with GA and BD results in a biomaterial with favorable properties for use as an aortic valve prosthesis.

Re-endothelialization has been recognized as a promising strategy to address the tissue hyperplasia and subsequent restenosis which are major complications associated with vascular implant/interventional titanium devices. However, the uncontrollable over-proliferation of smooth muscle cells (SMCs) limits the clinical application of numerous modified strategies. Herein, a novel modified strategy involving with a two-step anodic oxidation and annealing treatment was proposed to achieve rapid re-endothelialization function regulated by regular honeycomb nanotexture and specific anatase phase on the titanium surface. Theoretical calculation revealed that the presence of nanotexture reduced the polar component of surface energy, while the generation of anatase significantly enhanced the polar component and total surface energy. Meanwhile, the modified surface with regular nanotexture and anatase phase produced positive effect on the expression of CD31, VE-Cadherin and down-regulated α-SMA proteins expression, indicating excellent capacity of pro-endothelial regeneration and inhibition of SMCs proliferation and migration. One-month in vivo implantation in rabbit carotid arteries further confirmed that modified tube implant surface effectively accelerated confluent endothelial monolayer formation and promoted native-like endothelium tissue regeneration. By contrast, original titanium tube implant induced a disorganized tissue proliferation in the lumen with a high risk of restenosis. Collectively, this study opens us an alternative route to achieve the function that selectively promotes endothelial cells (ECs) growth and suppresses SMCs on the medical titanium surface, which has a great potential in facilitating re-endothelialization on the surface of blood-contacting titanium implant.