Glycoprotein M6B Interacts with TßRI to Activate TGF-ß-Smad2/3 Signaling and Promote Smooth Muscle Cell Differentiation.

Smooth muscle cells (SMCs), which form the walls of blood vessels, play an important role in vascular development and the pathogenic process of vascular remodeling. However, the molecular mechanisms governing SMC differentiation remain poorly understood. Glycoprotein M6B (GPM6B) is a four-transmembrane protein that belongs to the proteolipid protein family and is widely expressed in neurons, oligodendrocytes, and astrocytes. Previous studies have revealed that GPM6B plays a role in neuronal differentiation, myelination, and osteoblast differentiation. In the present study, we found that the GPM6B gene and protein expression levels were significantly upregulated during transforming growth factor-ß1 (TGF-ß1)-induced SMC differentiation. The knockdown of GPM6B resulted in the downregulation of SMC-specific marker expression and repressed the activation of Smad2/3 signaling. Moreover, GPM6B regulates SMC Differentiation by Controlling TGF-ß-Smad2/3 Signaling. Furthermore, we demonstrated that similar to p-Smad2/3, GPM6B was profoundly expressed and coexpressed with SMC differentiation markers in embryonic SMCs. Moreover, GPM6B can regulate the tightness between TßRI, TßRII, or Smad2/3 by directly binding to TßRI to activate Smad2/3 signaling during SMC differentiation, and activation of TGF-ß-Smad2/3 signaling also facilitate the expression of GPM6B. Taken together, these findings demonstrate that GPM6B plays a crucial role in SMC differentiation and regulates SMC differentiation through the activation of TGF-ß-Smad2/3 signaling via direct interactions with TßRI. This finding indicates that GPM6B is a potential target for deriving SMCs from stem cells in cardiovascular regenerative medicine. Stem Cells 2018 Stem Cells 2019;37:190-201.

12-Month clinical results of drug-coated balloons for de novo coronary lesion in vessels exceeding 3.0 mm.

The purpose of this observational study was to investigate the feasibility, initial safety, and efficacy of the SeQuent® Please DCB (B. Braun Melsungen, Germany) for patients with de novo coronary lesions in vessels exceeding 3.0 mm in a consecutive series of all comer percutaneous coronary intervention. A total of 120 patients (135 lesions) with de novo coronary lesions in vessels ≥ 3.0 mm treated with DCB were enrolled in this single-centre prospective observational study. The primary endpoint was target lesion failure (TLF), a composite endpoint of cardiac death, target vessel-myocardial infarction (TV-MI), and clinically driven target vessel revascularization (TLR) at 12 months. Safety endpoints included cardiac death, TV-MI, and definite target vessel thrombosis. 45.9% of the lesions were classified as complex (type B2/C). The reference vessel diameter was 3.09 ± 0.31 mm measured via quantitative coronary angiography analysis. Coronary dissections occurred in 42 patients (35.0%; Type A-B 14.1%; Type C 19.1%; Type D: 1.6%), two of which [1.6%; (type D dissection)] underwent bail-out stent implantation. 12-month follow-up was completed in 100% patients. The 12-month incidence of TLF was 3.4%. The clinically driven TLR occurred in four patients (3.4%). The incidence of TLR was low in patients without any detectable dissections, similar to those with dissections (3.8% vs. 2.5%; p = 0.146). No patient suffered cardiac death, TV-MI, or target vessel thrombosis. The study shows the feasibility, initial safety, and efficacy of coronary intervention using SeQuent® Please DCB for the treatment of patients with de novo lesion in vessels exceeding 3 mm. The study highlights that the coronary dissection (Type A-C) post DCB treatment occurs frequently but is safe at follow up.