%0 Journal Article
%T Alterations in Coronary Resistance Artery Network Geometry in Diabetes and the Role of Tenascin C.
%A Kiss A
%A Nadasy GL
%A Fees A
%A Arnold Z
%A Aykac I
%A Dostal C
%A Szabó GT
%A Szabó PL
%A Szekeres M
%A Pokreisz P
%A Hunyady L
%A Podesser BK
%J Rev Cardiovasc Med
%V 24
%N 1
%D 2023 Jan
%M 39076867
%F 4.43
%R 10.31083/j.rcm2401006
%X UNASSIGNED: Geometrical alterations in the coronary resistance artery network and the potential involvement of Tenascin C (TNC) extracellular matrix protein were investigated in diabetic and control mice.
UNASSIGNED: Diabetes was induced by streptozotocin (STZ) injections (n = 7-11 animals in each group) in Tenascin C KO (TNC KO) mice and their Wild type (A/J) littermates. After 16-18 weeks the heart was removed and the whole subsurface network of the left coronary artery was prepared (down to branches of 40 μ m outer diameter), in situ pressure-perfused and studied using video-microscopy. Outer and inner diameters, wall thicknesses and bifurcation angles were measured on whole network pictures reconstructed into collages at 1.7 μ m pixel resolutions.
UNASSIGNED: Diabetes induced abnormal morphological alterations including trifurcations, sharp bends of larger branches, and branches directed retrogradely (p < 0.001 by the χ 2 test). Networks of TNC KO mice tended to form early divisions producing parallelly running larger branches (p < 0.001 by the χ 2 probe). Networks of coronary resistance arteries were substantially more abundant in 100-180 μ m components, appearing in 2-5 mm flow distance from orifice in diabetes. This was accompanied by thickening of the wall of larger arterioles ( > 220 μ m) and thinning of the wall of smaller (100-140 μ m) arterioles (p < 0.001). Blood flow should cover larger distances in diabetic networks, but interestingly STZ-induced diabetes did not generate further geometrical changes in TNC KO mice.
UNASSIGNED: Diabetes promotes hypertrophic and hypotrophic vascular remodeling and induces vasculogenesis at well defined, specific positions of the coronary vasculature. TNC plays a pivotal role in the formation of coronary network geometry, and TNC deletion causes parallel fragmentation preventing diabetes-induced abnormal vascular morphologies.