Vascular Wall Progenitor Cells in Health and Disease

Abstract

The vasculature plays an indispensible role in organ development and maintenance of tissue homeostasis, such that disturbances to it impact greatly on developmental and postnatal health. Although cell turnover in healthy blood vessels is low, it increases considerably under pathological conditions. The principle sources for this phenomenon have long been considered to be the recruitment of cells from the peripheral circulation and the re-entry of mature cells in the vessel wall back into cell cycle. However, recent discoveries have also uncovered the presence of a range of multipotent and lineage-restricted progenitor cells in the mural layers of postnatal blood vessels, possessing high proliferative capacity and potential to generate endothelial, smooth muscle, hematopoietic or mesenchymal cell progeny. In particular, the tunica adventitia has emerged as a progenitor-rich compartment with niche-like characteristics that support and regulate vascular wall progenitor cells. Preliminary data indicate the involvement of some of these vascular wall progenitor cells in vascular disease states, adding weight to the notion that the adventitia is integral to vascular wall pathogenesis, and raising potential implications for clinical therapies. This review discusses the current body of evidence for the existence of vascular wall progenitor cell subpopulations from development to adulthood and addresses the gains made and significant challenges that lie ahead in trying to accurately delineate their identities, origins, regulatory pathways, and relevance to normal vascular structure and function, as well as disease.

Diabetic microangiopathy: Pathogenetic insights and novel therapeutic approaches

“…Over the past decade, there has been increasing evidence that the integrity of the vascular wall is maintained by diversified cell populations, dedicated to endothelial repair and angiogenesis [8,9,14,15]. Diabetic patients often show deterioration of those cell types, especially in the presence of other cardiovascular complications [13,16].…”

“…COX-2, which is induced by cytokines, mitogens and endotoxin, regulates the expression and activity of MMP-9 [78]. Although the role of COX-2 in atherothrombosis remains controversial [79], endothelial COX-2 and MMPs have been shown to co-localize in unstable plaques and the retina, where they play an essential role in angiogenesis and related complications, such as plaque destabilization [80], as well as proliferative diabetic retinopathy [6], both characterized by excessive angiogenesis [8,81]. MMP-9 is strongly induced by cytokines in macro-and microvascular endothelial cells, while MMP-2 is refractory to these stimuli or less markedly induced [82].…”

“…These include a dysregulated vessel regeneration and impaired function of vascular cells (i.e., endothelial cells (ECs), vascular smooth muscle cells (VSMCs), stromal cells, pericytes, inflammatory cells, circulating and tissue-resident vascular stem/progenitor cells), all involved in the maintenance of vascular homeostasis and permeability [8,9]. The present review summarizes recent advances in the research of cellular and molecular pathways of microvascular disease in diabetes, provides insights into pathogenic mechanisms of vascular damage in diabetes, and indicates potential new targets for prevention and treatment strategies.…”

The Plot Thickens Further for Type I Interferons in Atherosclerotic Disease

“…There is a controversy about whether they originate from circulating cells or from local tissue precursors. 10,11 In addition, a further step needs to be taken into how they affect atherosclerotic plaque development. One mouse study showed that mobilization of SMPCs promoted atherosclerotic plaque development and led to larger lesions.…”

Effects of Long-Term Type I Interferon on the Arterial Wall and Smooth Muscle Progenitor Cells Differentiation

“…the vascular wall, particularly the adventitia, is an alternative source of SMPC. 20 Adequate understanding the role of SMPC during the atherosclerotic progress is critical in developing new avenues for potential therapy.…”