Abstract-Remodeling of small arteries is essential in the long-term regulation of blood pressure and blood flow to specific organs or tissues. A large part of the change in vessel diameter may occur through non-growth-related reorganization of vessel wall components. The hypothesis was tested that tissue-type transglutaminase (tTG), a cross-linking enzyme, contributes to the inward remodeling of small arteries. The in vivo inward remodeling of rat mesenteric arteries, induced by low blood flow, was attenuated by inhibition of tTG. Rat skeletal muscle arteries expressed tTG, as identified by Western blot and immunostaining. In vitro, activation of these arteries with endothelin-1 resulted in inward remodeling, which was blocked by tTG inhibitors. Small arteries obtained from rats and pigs both showed inward remodeling after exposure to exogenous transglutaminase, which was inhibited by addition of a nitric oxide donor. Enhanced expression of tTG, induced by retinoic acid, increased inward remodeling of porcine coronary arteries kept in organ culture for 3 days. The activity of tTG was dependent on pressure. Inhibition of tTG reversed remodeling, causing a substantial increase in vessel diameter. In a collagen gel contraction assay, tTG determined the compaction of collagen by smooth muscle cells. Collectively, these data show that small artery remodeling associated with chronic vasoconstriction depends on tissue-type transglutaminase. This mechanism may reveal a novel therapeutic target for pathologies associated with inward remodeling of the resistance arteries. hronic alteration in the hemodynamic profile is associated with arterial remodeling. Both large and small arteries adapt to a reduction in blood flow with a decrease in lumen diameter, 1,2 and in several forms of hypertension, the wall-to-lumen ratio of arteries is increased. 3,4 Although hypertrophy of the vessel wall may contribute to this remodeling in larger arteries, in resistance arteries, it mainly involves a geometrical reorganization of wall components around a smaller lumen. 5 Thus, in essential hypertension, the reduction in lumen size of resistance arteries appears to be eutrophic, ie, without a change in the amount of wall material. 3 In the process of inward remodeling, the reorganization of smooth muscle cells, induced by chronic vasoconstriction, may be an early event. 6 Whereas inward remodeling is identified as an important risk factor for cardiovascular events, 7 the mechanisms that control blood vessel caliber under physiological and pathological conditions are incompletely understood.Tissue-type transglutaminase (tTG), also called transglutaminase type 2, belongs to a family of enzymes that includes coagulation factor XIII. tTG is ubiquitously expressed and present both within the cells and at the cell surface, where it associates with integrins. 8 The enzyme catalyzes the formation of an N⑀ (␥-glutamyl)lysine cross-link, a bond between a glutamine residue and the primary amino group of either a peptide-bound lysine or a polyamine. M...

Optical coherence tomography (OCT) can be used to visualize the arterial wall and atherosclerotic plaques with high resolution. In this study, we verified the application of OCT to the quantitative analysis of plaque structural dimensions and optical attenuation coefficients of the components. We assessed the effect of balloon dilation on the OCT signal from the medial layer of porcine carotid artery ex vivo. Imaging of human autopsy samples was performed from the luminal side with a high (3.5 microm axial and 7 microm lateral) resolution OCT system (approximately 800 nm) or a regular (15-20 microm axial and 20 microm lateral resolution) OCT system (approximately 1,300 nm). For each sample, dimensions were measured by histomorphometry and OCT, and the optical attenuation was measured. In a tissue culture set-up, porcine carotid arteries were dilated and the attenuation coefficients of the dilated segments were compared to a control segment for 4 h. Quantitative analysis showed a strong and significant correlation between OCT and histology cap thickness measurements for both OCT systems. For both systems, the measured attenuation coefficients for diffuse intimal thickening and lipid-rich regions differed significantly from that of calcified tissue. Balloon dilation induced a time-dependent increase in the attenuation coefficient, which may be attributed to the induction of apoptosis. In conclusion both the high and regular resolution OCT systems can image the atherosclerotic plaques precisely. Quantitative analysis of the OCT signals allowed in situ determination of the intrinsic optical attenuation coefficient for atherosclerotic tissue components within regions of interest, which can help to discriminate between plaque and arterial wall components.

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