Background: How the extracellular matrix (ECM) microenvironment modulates the contractile phenotype of vascular smooth muscle cells (VSMCs) and confers vascular homeostasis remains elusive. Methods: To explore the key ECM proteins in the maintenance of the contractile phenotype of VSMCs, we applied protein-protein interaction network analysis to explore novel ECM proteins associated with the VSMC phenotype. By combining in vitro and in vivo genetic mice vascular injury models, we identified nidogen-2, a basement membrane glycoprotein, as a key ECM protein for maintenance of vascular smooth muscle cell identity. Results: We collected a VSMC phenotype–related gene dataset by using Gene Ontology annotation combined with a literature search. A computational analysis of protein-protein interactions between ECM protein genes and the genes from the VSMC phenotype–related gene dataset revealed the candidate gene nidogen-2, a basement membrane glycoprotein involved in regulation of the VSMC phenotype. Indeed, nidogen-2–deficient VSMCs exhibited loss of contractile phenotype in vitro, and compared with wild-type mice, nidogen-2 ^{–/ –} mice showed aggravated post–wire injury neointima formation of carotid arteries. Further bioinformatics analysis, coimmunoprecipitation assays, and luciferase assays revealed that nidogen-2 specifically interacted with Jagged1, a conventional Notch ligand. Nidogen-2 maintained the VSMC contractile phenotype via Jagged1-Notch3 signaling but not Notch1 or Notch2 signaling. Nidogen-2 enhanced Jagged1 and Notch3 interaction and subsequent Notch3 activation. Reciprocally, Jagged1 and Notch3 interaction, signaling activation, and Jagged1-triggered VSMC differentiation were significantly repressed in nidogen-2–deficient VSMCs. In accordance, the suppressive effect of Jagged1 overexpression on neointima formation was attenuated in nidogen-2 ^–/– mice compared with wild-type mice. Conclusions: Nidogen-2 maintains the contractile phenotype of VSMCs through Jagged1-Notch3 signaling in vitro and in vivo. Nidogen-2 is required for Jagged1-Notch3 signaling.

Background: Vascular calcification is closely related to the all-cause mortality of cardiovascular events. Basement membrane protein nidogen-2 is a key component of the vascular extracellular matrix microenvironment and we recently found it is pivotal for the maintenance of contractile phenotype in vascular smooth muscle cells (VSMCs). However, whether nidogen-2 is involved in VSMCs osteochondrogenic transition and vascular calcification remains unclear. Methods: VSMCs was treated with high-phosphate to study VSMC calcification in vitro. Three different mice models (5/6 nephrectomy-induced chronic renal failure, cholecalciferol-overload, and periadventitially administered with CaCl ₂ ) were used to study vascular calcification in vivo. Membrane protein interactome, coimmunoprecipitation, flow cytometric binding assay, surface plasmon resonance, G protein signaling, VSMCs calcium assays were performed to clarify the phenotype and elucidate the molecular mechanisms. Results: Nidogen-2 protein levels were significantly reduced in calcified VSMCs and aortas from mice in different vascular calcification model. Nidogen-2 deficiency exacerbated high-phosphate-induced VSMC calcification, whereas the addition of purified nidogen-2 protein markedly alleviated VSMC calcification in vitro. Nidogen-2 ^-/- mice exhibited aggravated aorta calcification compared to wild-type (WT) mice in response to 5/6 nephrectomy, cholecalciferol-overload, and CaCl ₂ administration. Further unbiased coimmunoprecipitation and interactome analysis of purified nidogen-2 and membrane protein in VSMCs revealed that nidogen-2 directly binds to LGR4 (leucine-rich repeat G-protein-coupled receptor 4) with K _D value 26.77 nM. LGR4 deficiency in VSMCs in vitro or in vivo abolished the protective effect of nidogen-2 on vascular calcification. Of interest, nidogen-2 biased activated LGR4-Gαq-PKCα (protein kinase Cα)-AMPKα1 (AMP-activated protein kinase α1) signaling to counteract VSMCs osteogenic transition and mineralization. Conclusions: Nidogen-2 is a novel endogenous ligand of LGR4 that biased activated Gαq- PKCα-AMPKα1 signaling and inhibited vascular calcification.

Thoracic aortic dissection (TAD) is a life-threatening cardiovascular disease that is associated with high morbidity and mortality. The prevailing challenge in TAD monitoring and diagnosis is the lack of novel biomarkers. A significant and sustained reduction in plasma cartilage oligomeric matrix protein (COMP) levels was observed through a case control analysis conducted in 362 TAD patients and 136 controls. The protective role of COMP was assessed in two TAD mouse models. These data suggested that a decreased plasma COMP level might serve as a novel biomarker for TAD progression and COMP could suppress the development of TAD and ameliorate vascular pathogenesis.

Thoracoabdominal aortic aneurysm (TAAA) involves both the thoracic and abdominal aorta and surgical treatment requires reconstructing several important visceral branch arteries. Open surgery is considered the standard treatment for TAAA, but it carries high risks and many complications. With the advancement of endovascular techniques, endovascular repair of TAAA has gradually become a new trend in treatment. This article presents a case of a 61-year-old female with TAAA. The patient underwent a follow-up thoracoabdominal CTA after teratoma surgery, which revealed a thoracoabdominal aortic aneurysm (Crawford Type III) extending from the sixth intercostal space to 5 cm below the renal arteries. The challenge in treating this case lay in reconstructing the visceral arteries. The octopus technique, a type of parallel stenting, offers advantages but has inherent technical limitations, such as multiple access routes for simultaneous stent placement, the potential risk of gutter endoleaks, and mutual compression among parallel stents. To avoid these drawbacks, modifications to the octopus technique are necessary. We connected multiple small stent grafts side-by-side and end-to-end to a single branch of the main aortic stent graft. This improved design effectively circumvented the gutter endoleaks and stent compression issues, allowing for sequential visceral artery reconstruction through single upper limb access. This modified octopus technique closely aligns with the design concept of branched stents. This article aims to describe a case of complete endovascular reconstruction of TAAA using the modified octopus technique combined with the external branch technique, providing an in-depth analysis of the specific procedural steps and their clinical application value.

Thoracoabdominal aortic aneurysm (TAAA) involves both the thoracic and abdominal aorta and surgical treatment requires reconstructing several important visceral branch arteries. Open surgery is considered the standard treatment for TAAA, but it carries high risks and many complications. With the advancement of endovascular techniques, endovascular repair of TAAA has gradually become a new trend in treatment. This article presents a case of a 61-year-old female with TAAA. The patient underwent a follow-up thoracoabdominal CTA after teratoma surgery, which revealed a thoracoabdominal aortic aneurysm (Crawford Type III) extending from the sixth intercostal space to 5 cm below the renal arteries. The challenge in treating this case lay in reconstructing the visceral arteries. The octopus technique, a type of parallel stenting, offers advantages but has inherent technical limitations, such as multiple access routes for simultaneous stent placement, the potential risk of gutter endoleaks, and mutual compression among parallel stents. To avoid these drawbacks, modifications to the octopus technique are necessary. We connected multiple small stent grafts side-by-side and end-to-end to a single branch of the main aortic stent graft. This improved design effectively circumvented the gutter endoleaks and stent compression issues, allowing for sequential visceral artery reconstruction through single upper limb access. This modified octopus technique closely aligns with the design concept of branched stents. This article aims to describe a case of complete endovascular reconstruction of TAAA using the modified octopus technique combined with the external branch technique, providing an in-depth analysis of the specific procedural steps and their clinical application value.

Background: Type II endoleak (T2EL) remains a significant cause of reintervention after endovascular aneurysm repair (EVAR). Current strategies for T2EL management remain suboptimal with low long-term efficacy. Thus, this study aimed to evaluate the feasibility and outcomes of laparoscopic transperitoneal branch artery ligation for T2EL management. Methods: This study included 6 patients with persistent T2EL and aneurysm sac expansion who underwent laparoscopic ligation of the culprit vessels, including the inferior mesenteric, lumbar, and median sacral arteries, at our center between January 2021 and January 2024. Preoperative basic clinical characteristics, operative data, postoperative outcomes, and complications of the patients were recorded and analyzed. Results: The median operative time was 225 minutes (range: 120–360 min) with blood loss of 300 mL (range: 50–500 mL). All patients achieved complete ligation of targeted vessels (median of 5 vessels per patient), with 100% success for the inferior mesenteric artery (IMA) and 50% for the median sacral artery. One patient developed a lymphatic fistula that was managed conservatively. At a median follow-up of 13.5 months (range: 4–54 months), all patients exhibited sac regression (median reduction: 3.5 mm; range: 1–8 mm). Complete endoleak resolution was observed in 4 cases (66.7%), while 2 had asymptomatic persistent T2EL without expansion. No reinterventions or mortality occurred. Conclusions: Laparoscopic transperitoneal branch artery ligation represents a promising, albeit preliminary, option for managing embolization-refractory T2EL. Our findings suggest that laparoscopic T2EL repair may provide durable sac stabilization in selected patients; however, the limited sample size underscores the need for larger studies to clarify patient selection criteria and long-term durability.