Calcific aortic valve disease (CAVD) lacks effective drug therapy. This study integrated human valve transcriptomic datasets and tissue specimens, public single‐cell and spatial transcriptomics, primary human valvular interstitial cell (VIC) models, and ApoE ^−/− mice fed a high‐fat diet to define the role of KLF5 in VIC remodeling. KLF5 expression was reduced in calcified human valves and associated with hemodynamic severity; tissue and single‐cell analyses localized this reduction to VIC‐rich lesions and disease‐associated VIC states. In primary VICs, KLF5 overexpression suppressed, whereas KLF5 knockdown enhanced, osteogenic medium‐induced inflammatory signaling and mineralization. Systemic AAV‐mediated KLF5 overexpression attenuated valve dysfunction, leaflet thickening, mineral deposition, and BMP2 expression in ApoE ^−/− mice. Mechanistically, KLF5 loss increased cytosolic mtDNA accumulation and activated cGAS–STING and NLRP3‐associated signaling, whereas cGAS knockdown reduced downstream signaling and interferon‐stimulated gene induction. KLF5 directly activated the BNIP3 promoter and supported BNIP3‐mediated mitophagy. BNIP3 knockdown markedly reduced the ability of KLF5 overexpression to preserve mitophagic flux and restrain inflammatory signaling and mineralization, whereas BNIP3 re‐expression mitigated the corresponding phenotypes in KLF5‐deficient VICs. These findings identify a VIC‐centered KLF5–BNIP3 regulatory pathway that supports mitochondrial quality control and limits mtDNA‐sensitive sterile inflammation, providing a mechanistic rationale for future therapeutic investigation in CAVD.

Chronic respiratory diseases (CRDs) remain a major source of mortality and disability worldwide, yet current evidence on their long‐term burden in the WHO Western Pacific Region (WPR) is limited. This study assessed temporal trends, demographic disparities, subtype composition, and major modifiable risk factors for CRDs from 1990 to 2023 in the WPR membership fixed at the study endpoint (WPR‐37). Estimates were extracted from the IHME GBD 2023 results tool for the aggregate location “Western Pacific Region” (location ID 44568), comprising 37 WHO Member States and areas as of 31 December 2023; Indonesia was excluded. We analyzed incidence, prevalence, deaths, and disability‐adjusted life years (DALYs), reporting absolute numbers and age‐standardized rates (ASRs). Trends were quantified using estimated annual percentage change (EAPC). Attributable deaths and DALYs were assessed for tobacco smoking, air pollution, and occupational exposure. In 2023, CRDs in WPR‐37 accounted for 22.0 million incident cases, 155.9 million prevalent cases, 1.4 million deaths, and 29.9 million DALYs. Compared with 1990, absolute numbers increased across all indicators, whereas ASRs were stable or declined. Age‐standardized incidence and prevalence rates decreased modestly, whereas age‐standardized mortality and DALY rates declined more markedly, with EAPCs of −2.67% (95% confidence interval [CI]: −3.02 to −2.33) and −2.31% (95% CI: −2.56 to −2.05), respectively. The burden increased sharply with age, remained higher in males, and was dominated by chronic obstructive pulmonary disease, accounting for 75.3% of DALYs. Tobacco smoking and air pollution were the leading selected modifiable contributors, whereas six‐country comparisons showed marked regional heterogeneity. Although age‐standardized mortality and DALY rates declined substantially, the absolute burden continued to rise, mainly reflecting population growth and aging. The burden remained concentrated in older adults, males, and chronic obstructive pulmonary disease. These estimates describe WPR‐37 rather than the current 38‐member WPR.

Corrigendum: Clinical outcomes following surgical mitral valve plasty or replacement in patients with infectious endocarditis: A meta-analysis