01 January 2015 by Kurt R Stenmark, Michael Yeager

Contrasting hypotheses regarding origin and perpetuation of vascular remodeling and inflammation

Stenmark {KR},Yeager M,Riddle S,El Kasmi {KC},Frid {MG},Li M,{McKinsey} T.Targeting the adventitial microenvironment in pulmonary hypertension: A potential approach to therapy that considers epigenetic change. [Internet]. 2012 ;2:3. Available from:http://www.pulmonarycirculation.org/text.asp?2012/2/1/3/94817

Contrasting hypotheses regarding origin and perpetuation of vascular remodeling and inflammation. (A) Traditionally, remodeling and inflammation have been considered an "Inside/Out" response centered on endothelial injury, leukocyte/monocyte recruitment to the intima of blood vessels, followed by activation of medial smooth muscle cells. In this hypothesis, remodeling is largely thought to be mediated by endothelial cell activation, injury or death, abnormalities in endothelial-smooth muscle communication and resultant hyper-proliferation of either/or both cell types and recruitment of inflammatory cells, which are directed from the lumen of the pulmonary artery. (B) The "Outside-In" hypothesis suggests that vascular inflammation because of resident professional (dendritic cells, macrophages and lymphocytes) and nonprofessional (fibroblasts) immune cells occurs early and persists in the adventitia. Fibroblast activation, leukocyte and progenitor cell accumulation and retention lead to remodeling not only of the adventitia, but cause subsequent changes in the media and ultimately even the intima. Thus, the adventitia, as opposed to its' usual depiction (Panel A) of an unimportant simple support structure, is actually a highly cellular, metabolically active, regulatory compartment of the vessel wall, capable of controlling tone, structure, and inflammation from the outside-in.


Additional keywords: vascular remodeling,inside out,outside in,fibroblast,macrophages

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