Quantitative Imaging-Based Examination of Pericytes Controlling Endothelial Growth Dynamics and Angiogenesis.

Microvascular endothelial cell-mural cell interactions are instrumental in modulating both physiological and pathologic angiogenesis. Pericyte-endothelial cell communication through direct physical associations and secreted effectors comprises a bidirectional signal array that regulates vascular maturation and integrity. As endothelial cell proliferation, migration, and morphogenesis are key elements of vascular growth and remodeling during angiogenesis, we have developed novel preclinical systems for studying the roles of endothelial-mural cell dynamics on cell cycle entry and angiogenic activity in vitro.

Pericyte chemomechanics and the angiogenic switch: insights into the pathogenesis of proliferative diabetic retinopathy?

Purpose: To establish the regulatory roles that pericytes have in coordinating retinal endothelial cell (EC) growth and angiogenic potential.

Methods: Pericytes were derived from donor diabetic (DHuRP) or normal (NHuRP) human retinae, and characterized using vascular markers, coculture, contraction, morphogenesis, and proliferation assays. To investigate capillary "cross-talk," pericyte-endothelial coculture growth, and connexin-43 (Cx43) expression assays were performed.

Pericyte contractility controls endothelial cell cycle progression and sprouting: insights into angiogenic switch mechanics.

Microvascular stability and regulation of capillary tonus are regulated by pericytes and their interactions with endothelial cells (EC). While the RhoA/Rho kinase (ROCK) pathway has been implicated in modulation of pericyte contractility, in part via regulation of the myosin light chain phosphatase (MLCP), the mechanisms linking Rho GTPase activity with actomyosin-based contraction and the cytoskeleton are equivocal. Recently, the myosin phosphatase-RhoA-interacting protein (MRIP) was shown to mediate the RhoA/ROCK-directed MLCP inactivation in vascular smooth muscle.

Pericytes derived from adipose-derived stem cells protect against retinal vasculopathy.

Background: Retinal vasculopathies, including diabetic retinopathy (DR), threaten the vision of over 100 million people. Retinal pericytes are critical for microvascular control, supporting retinal endothelial cells via direct contact and paracrine mechanisms. With pericyte death or loss, endothelial dysfunction ensues, resulting in hypoxic insult, pathologic angiogenesis, and ultimately blindness.

Wound Healing Angiogenesis: Innovations and Challenges in Acute and Chronic Wound Healing.

Background: Formation of new blood vessels, by either angiogenesis or vasculogenesis, is critical for normal wound healing. Major processes in neovascularization include (i) growth-promoting or survival factors, (ii) proteolytic enzymes, (iii) activators of multiple differentiated and progenitor cell types, and (iv) permissible microenvironments. A central aim of wound healing research is to "convert" chronic, disease-impaired wounds into those that will heal.

JAGGED1 signaling regulates hemangioma stem cell-to-pericyte/vascular smooth muscle cell differentiation.

Objective: The aim of our study is to determine the cellular and molecular origin for the pericytes in infantile hemangioma (IH) and their functional role in the formation of pathological blood vessels.

Methods And Results: Here we show that IH-derived stem cells (HemSCs) form pericyte-like cells. With in vitro studies, we demonstrate that HemSC-to-pericyte differentiation depends on direct contact with endothelial cells.

Microvascular modifications in diabetic retinopathy.

Patients struggling with diabetes are at elevated risks for several sight-threatening diseases, including proliferative diabetic retinopathy (DR). DR manifests in two stages: first, the retinal microvasculature is compromised and capillary degeneration occurs; subsequently, an over-compensatory angiogenic response is initiated. Early changes in the retinal microcirculation include disruptions in blood flow, thickening of basement membrane, eventual loss of mural cells, and the genesis of acellular capillaries.

Inhibition of angiogenesis in vitro: a central role for beta-actin dependent cytoskeletal remodeling.

Endothelial cell migration and proliferation, central steps in both physiologic and pathologic angiogenesis, require cytoskeletal-dependent remodeling, which is, in large part, achieved by the dynamic regulation of the beta-actin network. Specifically, the beta-actin network has previously been shown to be (i) enriched in regions of highly motile cytoplasm, and (ii) modulated by its isoactin-specific barbed-end capping protein, beta cap73. We hypothesize that regulated over-expression of beta cap73 could disrupt angiogenesis by capping beta-actin-filament assembly thus inhibiting the incipient cellular migration and microvascular morphogenesis that ensues.

Myospryn is a direct transcriptional target for MEF2A that encodes a striated muscle, alpha-actinin-interacting, costamere-localized protein.

The full repertoire of proteins that comprise the striated muscle Z-disc and peripheral structures, such as the costamere, have yet to be discovered. Recent studies suggest that this elaborate protein network, which acts as a structural and signaling center for striated muscle, harbors factors that function as mechanosensors to ensure coordinated contractile activity. Mutations in genes whose products reside in this region often result in skeletal and cardio myopathies, demonstrating the importance of this macromolecular complex in muscle structure and function.