We describe a case of near-fatal asthma requiring extracorporeal membrane oxygenation (ECMO). The patient presented with severe respiratory distress, which was not responsive to conventional pharmacological therapy. The patient also failed to respond to mechanical ventilation and thus was placed on venovenous ECMO for temporary pulmonary support. A fiberoptic bronchoscopy revealed that large amounts of thick bronchial secretions had occluded the main bronchus, which suggested plastic bronchitis secondary to asthma. Aggressive airway hygiene with frequent bronchoscopies and application of biphasic cuirass ventilation for facilitation of secretion clearance were performed to improve the patient’s respiratory status. The patient achieved a full recovery and suffered no neurological sequelae. This case illustrates that aggressive pulmonary hygiene with ECMO is a useful therapy for patients with asthma-associated plastic bronchitis.

The ductus arteriosus (DA) immediately starts closing after birth. This dynamic process involves DA-specific properties, including highly differentiated smooth muscle, sparse elastic fibers, and intimal thickening (IT). Although several studies have demonstrated DA-specific gene expressions using animal tissues and human fetuses, the transcriptional profiles of the closing DA and the patent DA remain largely unknown. We performed transcriptome analysis using four human DA samples. The three closing DA samples exhibited typical DA morphology, but the patent DA exhibited aorta-like elastic lamellae and poorly formed IT. A cluster analysis revealed that samples were clearly divided into two major clusters, the closing DA and patent DA clusters, and showed distinct gene expression profiles in IT and the tunica media of the closing DA samples. Cardiac neural crest-related genes such as JAG1 were highly expressed in the tunica media and IT of the closing DA samples compared to the patent DA sample. Abundant protein expressions of jagged 1 and the differentiated smooth muscle marker calponin were observed in the closing DA samples but not in the patent DA sample. Second heart field-related genes such as ISL1 were enriched in the patent DA sample. These data indicate that the patent DA may have different cell lineages compared to the closing DA.

Many studies have revealed numerous potential biomarkers for atherosclerosis, but tissue-specific biomarkers are still needed. Recent lineage-tracing studies revealed that smooth muscle cells (SMCs) contribute substantially to plaque formation, and the loss of SMCs causes plaque vulnerability. We investigated the association of SMC-specific myosin heavy chain 11 (myosin-11) with atherosclerosis. Forty-five patients with atherosclerosis and 34 control subjects were recruited into our study. In the atherosclerosis patients, 35 patients had either coronary artery disease (CAD) or peripheral artery disease (PAD), and 10 had both CAD and PAD. Coronary arteries isolated from five patients were subjected to histological study. Circulating myosin-11 levels were higher in the CAD or PAD group than in controls. The area under the receiver operating characteristic curve of myosin-11 was 0.954. Circulating myosin-11 levels in the CAD and PAD group were higher than in the CAD or PAD group, while high-sensitivity C-reactive protein concentrations did not differ between these groups. Multinomial logistic regression analyses showed a significant association of myosin-11 levels with the presence of multiple atherosclerotic regions. Myosin-11 was expressed in the medial layer of human atherosclerotic lesions where apoptosis elevated. Circulating myosin-11 levels may be useful for detecting spatial expansion of atherosclerotic regions.

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is driven by progressive vascular remodeling, particularly smooth muscle cell (SMC) proliferation. Current combination vasodilator therapies have markedly improved outcomes; however, prognosis remains poor in subgroups such as patients with respiratory comorbidities. Elevation of intravascular hydrostatic pressure is a hallmark of IPAH, yet its direct role in pulmonary artery SMCs remains unclear. We aimed to identify pressure-responsive mediators using a newly developed hydrostatic pressurization system to model hypertensive hemodynamics. METHODS: Pulmonary artery SMCs from 4 patients with IPAH were exposed to high hydrostatic pressure (70/40 mm Hg, 60 bpm). Transcriptomic profiling identified differentially expressed genes, which were validated by quantitative polymerase chain reaction. Functional studies included PIEZO1 (piezo type mechanosensitive ion channel component 1) modulation, rhSTC1 (recombinant human stanniocalcin-1) treatment, bromodeoxyuridine incorporation, and Western blotting for cell-cycle regulators. Chronic hypoxia–induced pulmonary hypertension was assessed in wild-type and Stc1 ^–/– mice by hemodynamic and histological analyses, with or without intratracheal rhSTC1 administration. RESULTS: RNA sequencing revealed STC1 to be a pressure-induced gene in IPAH SMCs. PIEZO1 activation upregulated STC1 , whereas knockdown blunted this response. STC1 was upregulated in IPAH lungs, while rhSTC1 reduced pulmonary arterial SMC proliferation and increased p-p53, p21, and p27 expression. Stc1 ^–/– mice under hypoxia exhibited significantly higher right ventricular systolic pressure and greater pulmonary arterial medial thickness than wild-type mice. CD68-positive macrophages were increased in Stc1 ^–/– mice under normoxia and further elevated with hypoxia. Intratracheal administration of rhSTC1 attenuated PAH in wild-type and Stc1 ^–/– mice. CONCLUSIONS: Elevated hydrostatic pressure drives STC1 expression via PIEZO1, suggesting an adaptive but insufficient protective response in IPAH. Modulation of STC1 (stanniocalcin-1) may represent a potential therapeutic approach.