Pathological Conversion of Mouse Perivascular Adipose Tissue by Notch Activation.

Objective: Perivascular adipose tissue (PVAT) surrounding arteries supports healthy vascular function. During obesity, PVAT loses its vasoprotective effect. We study pathological conversion of PVAT, which involves molecular changes in protein profiles and functional changes in adipocytes.

Differentiation Capacity of Human Aortic Perivascular Adipose Progenitor Cells.

Adipose tissue is a rich source of multi-potent mesenchymal stem cells (MSC) capable of differentiating into osteogenic, adipogenic, and chondrogenic lineages. Adipogenic differentiation of progenitor cells is a major mechanism driving adipose tissue expansion and dysfunction in response to obesity. Understanding changes to perivascular adipose tissue (PVAT) is thus clinically relevant in metabolic disease.

Human Perivascular Adipose Tissue as a Regulator of the Vascular Microenvironment and Diseases of the Coronary Artery and Aorta.

Perivascular adipose tissue (PVAT) is an adipose depot that surrounds blood vessels in the human body and exerts local paracrine signaling. Under physiologically healthy conditions, PVAT has an anti-contractile effect on vessels, but in obesity this effect is lost. During metabolic disease, adiponectin secretion is dysregulated, influencing nitric oxide bioavailability and macrophage infiltration and inflammation, all of which mediate PVAT signaling.

Rab27a Regulates Human Perivascular Adipose Progenitor Cell Differentiation.

Purpose: Perivascular adipose tissue (PVAT) surrounds blood vessels and regulates vascular tone through paracrine secretion of cytokines. During conditions promoting cardiometabolic dysfunction, such as obesity, cytokine secretion is altered towards a proinflammatory and proatherogenic profile. Despite the clinical implications for cardiovascular disease, studies addressing the biology of human PVAT remain limited.

Development of a 3D bone marrow adipose tissue model.

Over the past twenty years, evidence has accumulated that biochemically and spatially defined networks of extracellular matrix, cellular components, and interactions dictate cellular differentiation, proliferation, and function in a variety of tissue and diseases. Modeling in vivo systems in vitro has been undeniably necessary, but when simplified 2D conditions rather than 3D in vitro models are used, the reliability and usefulness of the data derived from these models decreases. Thus, there is a pressing need to develop and validate reliable in vitro models to reproduce specific tissue-like structures and mimic functions and responses of cells in a more realistic manner for both drug screening/disease modeling and tissue regeneration applications.

Dynamic alterations in decoy VEGF receptor-1 stability regulate angiogenesis.

Blood vessel expansion is driven by sprouting angiogenesis of endothelial cells, and is essential for development, wound healing and disease. Membrane-localized vascular endothelial growth factor receptor-1 (mVEGFR1) is an endothelial cell-intrinsic decoy receptor that negatively modulates blood vessel morphogenesis. Here we show that dynamic regulation of mVEGFR1 stability and turnover in blood vessels impacts angiogenesis.

Antiangiogenic VEGF-A in peripheral artery disease.

Vascular endothelial growth factor A (VEGF-A) is a potent proangiogenic cytokine elevated in patients with peripheral artery disease (PAD). A new study links impaired vascular regrowth in PAD to increased expression of an antiangiogenic splice variant of VEGF-A.

A receptor-specific function for Notch2 in mediating vascular smooth muscle cell growth arrest through cyclin-dependent kinase inhibitor 1B.

Rationale: Deregulated vascular smooth muscle cell (VSMC) proliferation contributes to multiple vascular pathologies, and Notch signaling regulates VSMC phenotype.

Objective: Previous work focused on Notch1 and Notch3 in VSMC during vascular disease; however, the role of Notch2 is unknown. Because injured murine carotid arteries display increased Notch2 in VSMC as compared with uninjured arteries, we sought to understand the impact of Notch2 signaling in VSMCs.

Histone deacetylase activity selectively regulates notch-mediated smooth muscle differentiation in human vascular cells.

Background: Histone deacetylases (HDACs) modify smooth muscle cell (SMC) proliferation and affect neointimal lesion formation by regulating cell cycle progression. HDACs might also regulate SMC differentiation, although this is not as well characterized.

Methods And Results: Notch signaling activates SMC contractile markers and the differentiated phenotype in human aortic SMCs.

The miR-143/145 cluster is a novel transcriptional target of Jagged-1/Notch signaling in vascular smooth muscle cells.

Activation of Notch signaling by Jagged-1 (Jag-1) in vascular smooth muscle cells (VSMC) promotes a differentiated phenotype characterized by increased expression of contractile proteins. Recent studies show that microRNAs (miR)-143/145 regulates VSMC phenotype. The serum response factor (SRF)/myocardin complex binds to CArG sequences to activate miR-143/145 transcription, but no other regulators are known in VSMC.