Paracrine role of the vascular adventitia
In the early days of vascular biology research, the adventitia (the outermost layer of a blood vessel) was essentially ignored for its effect on vascular wall biology. It was largely considered to play a structural role in maintenance of vessel tensile strength and as a matrix from which innervating neurons and the vasa vasorum subserved large vessel function. Our seminal research in this area helped bring to light a paracrine signaling role for the adventitia in vascular homeostasis by demonstrating cross-talk between adventitial NADPH oxidase-derived ROS and remote cellular signaling effecting tone and medial hypertrophy and proliferation.
Di Wang H, Hope S, Du Y, Quinn MT, Cayatte A, Pagano PJ, Cohen RA. Paracrine role of adventitial superoxide anion in mediating spontaneous tone of the isolated rat aorta in angiotensin II-induced hypertension. Hypertension. 1999; 33(5):1225-32. PubMed PMID: 10334816
Rey FE, Li XC, Carretero OA, Garvin JL, Pagano PJ. Perivascular superoxide anion contributes to impairment of endothelium-dependent relaxation: role of gp91phox. Circulation. 2002; 106(19):2497-502. PubMed PMID: 12417549
Weaver M, Liu J, Pimentel D, Reddy DJ, Harding P, Peterson EL, Pagano PJ. Adventitial delivery of dominant-negative p67phox attenuates neointimal hyperplasia of the rat carotid artery. Am J Physiol, Heart Circ Physiol. 2006; 290(5): H1933-41. PubMed PMID: 16603705
Cascino T, Csanyi G, Al Ghouleh I, Montezano AC, Touyz RM, Haurani MJ, Pagano PJ. Adventitia-derived hydrogen peroxide impairs relaxation of the rat carotid artery via smooth muscle cell p38 mitogen-activated protein kinase. Antioxid Redox Signal. 2011; 15(6):1507-15. PubMed PMID: 21126185, PMCID: PMC3151421