Doo Sun Sim

Oh S, et al. Korean Circ J. 2027 ;57:e17. https://doi.org/10.4070/kcj.2025.0522

Vascular calcification is an actively regulated process driven by vascular smooth muscle cell (VSMC) osteogenic reprogramming and promoted by oxidative stress and extracellular matrix remodeling. We investigated whether the novel histone deacetylase inhibitor YAK577 mitigates calcification by modulating an MMP14–NOX2/ROS-associated pathway in calcification medium (CM)-treated VSMCs and a vitamin D₃-induced arterial calcification model in 8-week-old male C57BL/6N mice. Calcification was assessed by Alizarin Red S/von Kossa staining and calcium quantification; osteogenic markers (BMP2, RUNX2, MSX2) and MMPs were examined by qRT-PCR and immunoblotting; intracellular ROS was measured by DHE staining with N-acetylcysteine as an antioxidant control; and MMP14 was manipulated by siRNA knockdown or plasmid overexpression. YAK577 was non-cytotoxic at effective concentrations and reduced CM-induced calcium deposition and osteogenic marker expression. YAK577 reduced MMP14 expression and suppressed CM-induced NOX2/p47phox activation and ROS accumulation, while GSK2795039 attenuated CM-induced DHE fluorescence. MMP14 silencing attenuated, whereas MMP14 overexpression enhanced, osteogenic signaling and increased NOX2. In vivo, YAK577 reduced vitamin D₃-induced aortic calcium burden, histological calcification, and the expression of MMP14, NOX2, and osteogenic markers. These data support a working model in which YAK577 alleviates vascular calcification, at least in part, by suppressing an MMP14-associated NOX2/p47phox–ROS axis.

Background: The impact of prior antiplatelet exposure on outcomes of acute myocardial infarction remains unclear, particularly in East Asian populations with distinct antithrombotic response profiles. Methods: This retrospective cohort study analyzed 29 281 patients with acute myocardial infarction from 2 nationwide Korean registries. After excluding patients with atrial fibrillation, prior coronary artery disease, heart failure, cerebrovascular accident, or thrombolysis and those discharged on oral anticoagulants, 21 304 patients were categorized into previous‐user and nonuser groups. Propensity score matching was performed to adjust for baseline differences. The primary outcome was 3‐year major adverse cardiac and cerebrovascular events. Results: Previous users were older and had more comorbidities and angiographic complexity. Unadjusted analysis showed higher major adverse cardiac and cerebrovascular event rates in previous users, but the difference attenuated after propensity score matching in both the overall matched (adjusted hazard ratio [HR], 0.967 [95% CI, 0.850–1.100]) and selected population (adjusted HR, 1.036 [95% CI, 0.847–1.267]). All‐cause death remained slightly elevated in the overall matched cohort (HR, 1.204 [95% CI, 1.004–1.443]) but not in the selected population. In‐hospital outcomes and platelet reactivity findings supported the high‐risk profile of prior users. Conclusions: Prior antiplatelet exposure was associated with a higher‐risk clinical phenotype among patients with acute myocardial infarction, but this relationship was not independent after adjustment for baseline differences. These findings should be interpreted as hypothesis generating and underscore the importance of individualized antithrombotic strategies tailored to risk profiles, particularly in East Asian populations.

Background: Conventional drug-eluting stents suppress neointimal hyperplasia but delay re-endothelialization, raising long-term safety concerns. This study developed and evaluated a sirolimus–WKYMVm eluting stent (S-WES) to simultaneously promote re-endothelialization and suppress neointimal hyperplasia. Methods: Sirolimus-eluting stents (SES), WKYMVm-eluting stents (WES), and S-WES were fabricated using electrospray. Surface morphology was characterized via scanning electron microscopy (SEM), and in vitro drug-release kinetics were determined using high-performance liquid chromatography. Biological efficacy was assessed using human umbilical vein endothelial cell (HUVEC) and smooth muscle cell (SMC) assays. In vivo performance was evaluated over 4 weeks, followed by optical coherence tomography (OCT) and histopathological analysis. Results: SEM analysis showed that S-WES had a uniform, crack-free polymer coating. Each stent was consistently loaded with sirolimus (105.15 ± 25.54 μg) and WKYMVm (1.07 ± 0.18 μg), yielding a dual drug-release profile. WKYMVm was almost completely released within 7 days, whereas sirolimus showed sustained release (day 1: 22.43 ± 5.32%, day 28: 94.38 ± 4.11%). In vitro assays showed that sirolimus suppressed SMC migration and HUVEC proliferation, while WKYMVm significantly enhanced HUVEC proliferation. In vivo OCT revealed reduced neointimal hyperplasia in the S-WES group (29.64 ± 8.66 μm²) compared with SES (34.65 ± 7.50 μm²; p = 0.041). Histopathology and immunohistology showed reduced stenosis ratio (28.39 ± 6.84%), decreased α-SMA expression, and increased VE-cadherin, CD31-positive endothelial coverage in the S-WES group. Conclusion: The sirolimus–WKYMVm dual-drug stent enhances re-endothelialization and inhibits neointimal hyperplasia, thereby offering a promising strategy for improving the efficacy and long-term safety of cardiovascular stents.

Cho KH, et al. J Lipid Atheroscler. 2026 May;15(2):361-373. https://doi.org/10.12997/jla.2026.15.2.361

Honda S, et al. J Cardiovasc Interv. 2026 ;5:e22. https://doi.org/10.54912/jci.2025.0047

Cho KH, et al. J Korean Med Sci. 2026 Feb;41:e74. https://doi.org/10.3346/jkms.2026.41.e74

Ahn JH, et al. J Korean Med Sci. 2025 Aug;41:e2. https://doi.org/10.3346/jkms.2026.41.e2