Differential distribution of vasa vasorum in different vascular beds in humans



      Vasa vasorum (VV) have been implicated to play a role in the pathogenesis of atherosclerosis. This study was designed to describe the distribution of VV density in different vascular beds in humans and to investigate the association between VV density and the known distribution of atherosclerosis in human arteries.


      Forty-two human arteries, harvested at autopsy or after explantation, were analyzed by three-dimensional microscopic-computed tomography (micro-CT). VV density, endothelial-surface-fraction (Σ VV endothelial-surface-area/vessel-wall-volume) and vascular-area-fraction (Σ VV area/vessel-wall-area) were calculated for coronary, renal and femoral arteries. Representatively five coronary, renal and femoral arteries were stained for endothelial cells (von Willebrand-Factor), macrophages (CD68), vascular endothelial growth factor (VEGF) and collagen (Sirius Red).


      Coronary arteries showed a higher VV density compared to renal and femoral arteries (2.12 ± 0.26 n/mm2 versus 0.61 ± 0.06 n/mm2 and 0.66 ± 0.11 n/mm2; P < 0.05 for both) as well as a higher endothelial-surface-fraction and vascular-area-fraction.
      Histology showed a positive correlation between histologically derived VV density and CD68-positive cells/area (r = 0.54, P < 0.01), VEGF-immunoreactivity/area (r = 0.55, P < 0.01) and a negative correlation between VV density and collagen I content (r = 0.66, P < 0.05).


      This micro-CT study highlights a higher VV density in coronary than in peripheral arteries, supporting the relation between VV density and the susceptibility to atherosclerosis in different vascular beds in humans.


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        • Ross R.
        Atherosclerosis—an inflammatory disease.
        N Engl J Med. 1999; 340: 115-126
        • Pasterkamp G.
        • Schoneveld A.H.
        • Hillen B.
        • et al.
        Is plaque formation in the common carotid artery representative for plaque formation and luminal stenosis in other atherosclerotic peripheral arteries? A post mortem study.
        Atherosclerosis. 1998; 137: 205-210
      1. American Heart Association. Heart disease and stroke statistics—2006 Update. Am Heart Assoc 2006.

        • Vink A.
        • Schoneveld A.H.
        • Poppen M.
        • et al.
        Morphometric and immunohistochemical characterization of the intimal layer throughout the arterial system of elderly humans.
        J Anat. 2002; 200: 97-103
        • Barger A.C.
        • Beeuwkes Jr.III, R.
        • Lainey L.L.
        • Silverman K.J.
        Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis.
        N Engl J Med. 1984; 310: 175-177
        • Kumamoto M.
        • Nakashima Y.
        • Sueishi K.
        Intimal neovascularization in human coronary atherosclerosis: its origin and pathophysiological significance.
        Hum Pathol. 1995; 26: 450-456
        • Herrmann J.
        • Lerman L.O.
        • Rodriguez-Porcel M.
        • et al.
        Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia.
        Cardiovasc Res. 2001; 51: 762-766
        • Scotland R.S.
        • Vallance P.J.
        • Ahluwalia A.
        Endogenous factors involved in regulation of tone of arterial vasa vasorum: implications for conduit vessel physiology.
        Cardiovasc Res. 2000; 46: 403-411
        • Kaiser M.
        • Younge B.
        • Bjornsson J.
        • Goronzy J.J.
        • Weyand C.M.
        Formation of new vasa vasorum in vasculitis. Production of angiogenic cytokines by multinucleated giant cells.
        Am J Pathol. 1999; 155: 765-774
        • Moulton K.S.
        • Heller E.
        • Konerding M.A.
        • et al.
        Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice.
        Circulation. 1999; 99: 1726-1732
        • Moulton K.S.
        • Vakili K.
        • Zurakowski D.
        • et al.
        Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis.
        Proc Natl Acad Sci U.S.A. 2003; 100: 4736-4741
        • Kwon H.M.
        • Sangiorgi G.
        • Ritman E.L.
        • et al.
        Enhanced coronary vasa vasorum neovascularization in experimental hypercholesterolemia.
        J Clin Invest. 1998; 101: 1551-1556
        • Gossl M.
        • Rosol M.
        • Malyar N.M.
        • et al.
        Functional anatomy and hemodynamic characteristics of vasa vasorum in the walls of porcine coronary arteries.
        Anat Rec A Discov Mol Cell Evol Biol. 2003; 272: 526-537
        • Gossl M.
        • Versari D.
        • Mannheim D.
        • et al.
        Increased spatial vasa vasorum density in the proximal LAD in hypercholesterolemia—implications for vulnerable plaque-development.
        Atherosclerosis. 2007; 192: 246-252
        • Galili O.
        • Herrmann J.
        • Woodrum J.
        • et al.
        Adventitial vasa vasorum heterogeneity among different vascular beds.
        J Vasc Surg. 2004; 40: 529-535
        • Stary H.C.
        Natural history and histological classification of atherosclerotic lesions: an update.
        Arterioscler Thromb Vasc Biol. 2000; 20: 1177-1178
        • Herrmann J.
        • Samee S.
        • Chade A.
        • et al.
        Differential effect of experimental hypertension and hypercholesterolemia on adventitial remodeling.
        Arterioscler Thromb Vasc Biol. 2005; 25: 447-453
        • Versari D.
        • Herrmann J.
        • Gossl M.
        • et al.
        Dysregulation of the ubiquitin–proteasome system in human carotid atherosclerosis.
        Arterioscler Thromb Vasc Biol. 2006; 26: 2132-2139
        • Reardon C.A.
        • Blachowicz L.
        • Lukens J.
        • Nissenbaum M.
        • Getz G.S.
        Genetic background selectively influences innominate artery atherosclerosis: immune system deficiency as a probe.
        Arterioscler Thromb Vasc Biol. 2003; 23: 1449-1454
        • Witting P.K.
        • Pettersson K.
        • Letters J.
        • Stocker R.
        Site-specific antiatherogenic effect of probucol in apolipoprotein E-deficient mice.
        Arterioscler Thromb Vasc Biol. 2000; 20: E26-E33
        • Glagov S.
        Mechanical stresses on vessels and the non-uniform distribution of atherosclerosis.
        Med Clin North Am. 1973; 57: 63-77
        • Caro C.G.
        • Fitz-Gerald J.M.
        • Schroter R.C.
        Arterial wall shear and distribution of early atheroma in man.
        Nature. 1969; 223: 1159-1160
        • de Boer O.J.
        • van der Wal A.C.
        • Teeling P.
        • Becker A.E.
        Leucocyte recruitment in rupture prone regions of lipid-rich plaques: a prominent role for neovascularization?.
        Cardiovasc Res. 1999; 41: 443-449
        • Virmani R.
        • Kolodgie F.D.
        • Burke A.P.
        • et al.
        Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage.
        Arterioscler Thromb Vasc Biol. 2005; 25: 2054-2061
        • Langheinrich A.C.
        • Michniewicz A.
        • Bohle R.M.
        • Ritman E.L.
        Vasa vasorum neovascularization and lesion distribution among different vascular beds in ApoE−/−/LDL−/− double knockout mice.
        Atherosclerosis. 2007; 191: 73-81
        • Barker S.G.
        • Talbert A.
        • Cottam S.
        • Baskerville P.A.
        • Martin J.F.
        Arterial intimal hyperplasia after occlusion of the adventitial vasa vasorum in the pig.
        Arterioscler Thromb. 1993; 13: 70-77
        • Yun A.J.
        • Doux J.D.
        • Bazar K.A.
        • Lee P.Y.
        Adventitial dysfunction: an evolutionary model for understanding atherosclerosis.
        Med Hypotheses. 2005; 65: 962-965
        • Hu C.L.
        • Xiang J.Z.
        • Hu F.F.
        • Huang C.X.
        Adventitial inflammation: a possible pathogenic link to the instability of atherosclerotic plaque.
        Med Hypotheses. 2007; 68: 1262-1264
        • Nikol S.
        • Pelisek J.
        • Engelmann M.G.
        • et al.
        Vascular endothelial growth factor (VEGF165) and its influence on angiogenesis versus arteriogenesis in different vascular beds.
        J Endovasc Ther. 2002; 9: 842-854
        • Mitola S.
        • Brenchio B.
        • Piccinini M.
        • et al.
        Type I collagen limits VEGFR-2 signaling by a SHP2 protein-tyrosine phosphatase-dependent mechanism 1.
        Circ Res. 2006; 98: 45-54