Impaired adaptive vascular growth in hypercholesterolemic rabbit

Occlusive arterial disease stimulates compensatory growth of pre- existent and new arterial channels which help to maintain organ perfusion. Previous studies characterizing compensatory or collateral vascular growth have been performed in normocholesterolemic animals. Because hyperlipidemic states alter vascular regulation, it remains to be demonstrated that the capacity of the vasculature to undergo compensatory growth is preserved in the presence of dyslipidemic vascular injury. To assess effects of hypercholesterolemia on vascular growth, arterial supply to the ear of rabbits with (n = 13) or without hypercholesterolemia (n= 14) was surgically restricted. Compensatory growth of residual arteries and distal microvessels was evaluated using quantitative angiographic and microanatomic methods. Lumen-expanding hyperplasic arterial remodeling and distal microvascular proliferation induced by arterial restriction were assessed by independent techniques including in vivo microangiography, laser Doppler flowmetry, quantitative histometry, and thymidine incorporation. Compared with controls, hypercholesterolemic rabbits exhibited depressions in all arterial and capillary growth indexes. Microvascular proliferation in hypercholesterolemic rabbits was less than 20% of control. Results demonstrate for the first time that an atherogenic dyslipidemia may limit compensatory macro-and microvascular growth in response to arterial restriction, a phenomenon that could play an important role in the pathophysiology of atherosclerotic occlusive artery disease.