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The effects of recombinant semaphorin 3A (Sema3A) on myocardial contractility and electrical remodeling in mice with isoproterenol (ISP)-induced heart failure were investigated.C57BL/6J mice intraperitoneally received ISP (480 mg/kg/day, ISP group; n = 24) or saline (control group; n = 31) for 14 days. Twenty-one ISP-treated mice received 0.5 mg/kg Sema3A intravenously on days 7 and 11 (ISP+Sema3A group). The sympathetic nervous system was activated upon ISP treatment, but was reduced upon Sema3A administration. Greater myocardial tissue fibrosis was observed in the ISP group than in the control group. However, fibrosis was not significantly different between the ISP+Sema3A and control groups. Fractional shortening of the left ventricle was lower in the ISP group than in the control group and was restored in the ISP+Sema3A group (control, 53 ± 8%; ISP, 37 ± 7%; ISP+Sema3A, 48 ± 3%; P < 0.05). Monophasic action potential duration at 20% repolarization (MAPD20) was prolonged in the ISP group (compared to control group), but this was reversed upon Sema3A administration (control, 29 ± 3 ms; ISP, 35 ± 6 ms; ISP+Sema3A, 29 ± 3 ms; P < 0.05). qPCR revealed Kv4.3, KChIP2, and SERCA2 downregulation in the ISP group and upregulation in the ISP+Sema3A group; however, Western blotting revealed similar changes only for Kv4.3 (P < 0.05).Intravenous Sema3A may maintain myocardial contractility by suppressing the sympathetic innervation of the myocardium and reducing myocardial tissue damage, in addition to restoring MAPD via Kv4.3 upregulation.

Pathological changes after third-generation drug-eluting stent implantation remain unclear. We compared the tissue responses of coronary arteries after the implantation of third-generation abluminal biodegradable-polymer everolimus-eluting stent (3rd EES) and second-generation durable-polymer EES (2nd EES) using autopsy specimens and an atherosclerotic porcine model. We compared the histology of stented coronary arteries obtained by autopsy performed 1–10 months after 3rd EES (n (number of cases) = 4, stent-implanted period of 3–7 months) and 2nd EES (n (number of cases) = 9, stent-implanted period of 1–10 months) implantations. The ratio of covered stent struts was higher with 3rd EESs than with 2nd EESs (3rd; 0.824 ± 0.032 vs. 2nd; 0.736 ± 0.022, p = 0.035). Low-density lipoprotein receptor knockout minipigs were stented with 3rd or 2nd EES in the coronary arteries and the stented regions were investigated. The fibrin deposition around the 2nd EES was more prominent. Additionally, higher density of smooth muscle cells was confirmed after the 3rd EES implantation. Pathological examination after the 3rd EES demonstrated a combination of less fibrin deposition and more rapid acquisition of well-developed neointima as compared to the 2nd EES at autopsy and the atherosclerotic porcine model.

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Aims: Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition with a poor prognosis in which the pulmonary arteries are occluded by organized thrombi. P ulmonary thromboendarterectomy (PEA) is an effective treatment for CTEPH; however, the literature on its histopathological examination is lacking. This study aimed to investigate the histopathological findings and protein and gene expression in PEA specimens, establish an optimal histopathological evaluation method, and clarify the mechanisms of thrombus organization and disease progression in CTEPH. Methods: In total, 50 patients with CTEPH who underwent PEA were analyzed. The patients were categorized according to their clinical data into two groups: good and poor postoperative courses. The relationship between their histopathological findings and the clinical course was examined. Immunohistochemical studies confirmed the expression of oxidants, antioxidants, and s mooth muscle cell (SMC) differentiation markers and their changes during the progression of thrombus organization. The mRNA expression analysis of 102 samples from 27 cases included oxidants, antioxidants, and vasoconstrictor endothelin-1.Results: In the PEA specimens, colander-like lesions (aggregations of recanalized blood vessels with welldifferentiated SMCs) were significantly more common in the good postoperative course group than in the poor postoperative course group; analysis of proteins and genes proposed that oxidative and antioxidant mechanisms were involved. In the colander-like lesions, there was an increase in endothelin-1 mRNA and protein expression of endothelin receptor A.Conclusions: Colander-like lesions in PEA specimens must be identified. Additionally, SMC differentiation in recanalized vessels and the expression of vasoconstrictors and their receptors may contribute to the progression of CTEPH.