Survivin modulates stiffness-induced vascular smooth muscle cell motility.

Arterial stiffness is a key contributor to cardiovascular diseases, including atherosclerosis, restenosis, and coronary artery disease, it has been characterized to be associated with the aberrant migration of vascular smooth muscle cells (VSMCs). However, the underlying molecular mechanisms driving VSMC migration in stiff environments remain incompletely understood. We recently demonstrated that survivin, a member of the inhibitor of apoptosis protein family, is highly expressed in both mouse and human VSMCs cultured on stiff polyacrylamide hydrogels, where it modulates stiffness-mediated cell cycle progression and proliferation.

FAK and p130Cas Modulate Stiffness-Mediated Early Transcription and Cellular Metabolism.

Cellular metabolism is influenced by the stiffness of the extracellular matrix. Focal adhesion kinase (FAK) and its binding partner, p130Cas, transmit biomechanical signals, such as substrate stiffness, to the cell to regulate a variety of cellular responses, but their roles in early transcriptional and metabolic responses remain largely unexplored. We cultured mouse embryonic fibroblasts with or without siRNA-mediated FAK or p130Cas knockdown and assessed the early transcriptional responses of these cells to placement on soft and stiff substrates by RNA sequencing and bioinformatics analyses.

Transcriptomic and Multi-scale Network Analyses Reveal Key Drivers of Cardiovascular Disease.

Cardiovascular diseases (CVDs) and pathologies are often driven by changes in molecular signaling and communication, as well as in cellular and tissue components, particularly those involving the extracellular matrix (ECM), cytoskeleton, and immune response. The fine-wire vascular injury model is commonly used to study neointimal hyperplasia and vessel stiffening, but it is not typically considered a model for CVDs. In this paper, we hypothesize that vascular injury induces changes in gene expression, molecular communication, and biological processes similar to those observed in CVDs at both the transcriptome and protein levels.

Epigenetic Dynamics in Meniscus Cell Migration and its Zonal Dependency in Response to Inflammatory Conditions: Implications for Regeneration Strategies.

Meniscus injuries pose significant challenges in clinical settings, primarily due to the intrinsic heterogeneity of the tissue and the limited efficacy of current treatments. Endogenous cell migration is crucial for the healing process, yet the regulatory mechanisms of meniscus cell migration and its zonal dependency within the meniscus are not fully understood. Thus, this study investigates the role of epigenetic mechanisms in governing meniscus cell migration under inflammatory conditions, with a focus on their implications for injury healing and regeneration.

Loss-of-function G6PD variant moderated high-fat diet-induced obesity, adipocyte hypertrophy, and fatty liver in male rats.

Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases are still obscure and treatment is inadequate. We hypothesized that increased , glucose-6-phosphate dehydrogenase (G6PD), the key rate-limiting enzyme in the pentose shunt, is critical in evoking metabolic reprogramming in multiple organs and is a significant contributor to the pathogenesis of liver and cardiovascular diseases.

FAK and p130Cas modulate stiffness-mediated early transcription and cellular metabolism.

Cellular metabolism is influenced by the stiffness of the extracellular matrix. Focal adhesion kinase (FAK) and its binding partner, p130Cas, transmit biomechanical signals about substrate stiffness to the cell to regulate a variety of cellular responses, but their roles in early transcriptional and metabolic responses remain largely unexplored. We cultured mouse embryonic fibroblasts with or without siRNA-mediated FAK or p130Cas knockdown and assessed the early transcriptional responses of these cells to placement on soft and stiff substrates by RNA sequencing and bioinformatics analyses.

Survivin as a mediator of stiffness-induced cell cycle progression and proliferation of vascular smooth muscle cells.

Stiffened arteries are a pathology of atherosclerosis, hypertension, and coronary artery disease and a key risk factor for cardiovascular disease events. The increased stiffness of arteries triggers a phenotypic switch, hypermigration, and hyperproliferation of vascular smooth muscle cells (VSMCs), leading to neointimal hyperplasia and accelerated neointima formation. However, the mechanism underlying this trigger remains unknown.

Survivin regulates intracellular stiffness and extracellular matrix production in vascular smooth muscle cells.

Vascular dysfunction is a common cause of cardiovascular diseases characterized by the narrowing and stiffening of arteries, such as atherosclerosis, restenosis, and hypertension. Arterial narrowing results from the aberrant proliferation of vascular smooth muscle cells (VSMCs) and their increased synthesis and deposition of extracellular matrix (ECM) proteins. These, in turn, are modulated by arterial stiffness, but the mechanism for this is not fully understood.