Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice.

Aortic aneurysms are dilatations of the aorta that can rupture when left untreated. We used the aneurysmal Fibulin-4 mouse model to further unravel the underlying mechanisms of aneurysm formation. RNA sequencing of 3-month-old Fibulin-4 aortas revealed significant upregulation of senescence-associated secretory phenotype (SASP) factors and key senescence factors, indicating the involvement of senescence.

Hybrid Molecular and Functional Micro-CT Imaging Reveals Increased Myocardial Apoptosis Preceding Cardiac Failure in Progeroid Ercc1 Mice.

Purpose: In this study, we explored the role of apoptosis as a potential biomarker for cardiac failure using functional micro-CT and fluorescence molecular tomography (FMT) imaging techniques in Ercc1 mutant mice. Ercc1 is involved in multiple DNA repair pathways, and its mutations contribute to accelerated aging phenotypes in both humans and mice, due to the accumulation of DNA lesions that impair vital DNA functions. We previously found that systemic mutations and cardiomyocyte-restricted deletion of Ercc1 in mice results in left ventricular (LV) dysfunction at older age.

Pre-Operative Fasting Provides Long Term Protection Against Chronic Renal Damage Induced by Ischaemia Reperfusion Injury in Wild Type and Aneurysm Prone Fibulin-4 Mice.

Objective: Renal ischaemia reperfusion injury (IRI) is inevitable during open repair of pararenal aortic aneurysms. Pre-operative fasting potently increases resistance against IRI. The effect of fasting on IRI was examined in a hypomorphic Fibulin-4 mouse model (Fibulin-4), which is predisposed to develop aortic aneurysms.

Inflammation and TGF-β Signaling Differ between Abdominal Aneurysms and Occlusive Disease.

Abdominal aortic aneurysms (AAA), are usually asymptomatic until rupture causes fatal bleeding, posing a major vascular health problem. AAAs are associated with advanced age, male gender, and cardiovascular risk factors (e.g.

Fibulin-4 deficiency differentially affects cytoskeleton structure and dynamics as well as TGFβ signaling.

Fibulin-4 is an extracellular matrix (ECM) protein essential for elastogenesis and mutations in this protein lead to aneurysm formation. In this study, we isolated vascular smooth muscle cells (VSMCs) from mice with reduced fibulin-4 protein expression (Fibulin-4) and from mice with a smooth muscle cell specific deletion of the Fibulin-4 gene (Fibulin-4/SM22Cre). We subsequently analyzed and compared the molecular consequences of reduced Fibulin-4 expression versus total ablation of Fibulin-4 expression with regard to effects on the SMC specific contractile machinery, cellular migration and TGFβ signaling.