Regular transient limb ischemia prevents atherosclerosis progression in hypercholesterolemic rabbits

Abstract

Background: Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits. Methods: Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups ( n = 7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test. Results: Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = –2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = –2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = –2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = –2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049). Conclusion: In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.

Therapeutic Effects of Interventional Therapy and Conservative Therapy on Lower Extremity Arteriosclerosis Obliterans and Risk Factors for Prognosis

“…Similarly, it has recently been reported that the incidence rate of ASO rose with increasing age, particularly in people aged >70 years old [11]. It has been confirmed that interventional therapy was significantly superior to conservative therapy in terms of clinical effect and prognosis [12]. Smoking increases the incidence rate of vascular restenosis, so the risks of severe lower limb ischemia and amputation rise.…”

Sophisticated Prediction of Carotid-Plaque Vulnerability by Nanocluster Sensitized High-resolution Vessel-Wall-Imaging Profile in Rabbit Atherosclerotic Model

“…Although the high sensitivity of the HR-VWI-based molecular image method permits the detection of subtle morphological and physiological changes of AS plaque with small sample sizes, this animal experiment still suffers from several limitations including essential differences in disease progression from humans, lack of external validation for clinical management, and long duration to assess disease progression. [28][29][30] Here, the concept of triangulation by image-evaluating, histology validation, and statistical analysis were applied to increase confidence that an objective exact method was correctly conducted.…”

Regular transient limb ischemia protects endothelial function against hypercholesterolemic damage in rabbits

“…Our findings also provided preliminary evidence of the mechanism underlying the preventive effect of RTLI on atherosclerosis, which we had detected in our previous study. 25 Various pharmacological interventions improve EDV, including the use of antioxidant vitamins and endothelial nitric oxide synthase (eNOS) cofactor tetrahydrobiopterin (BH4). [35][36][37] Endothelial function can also be improved by lifestyle changes, including physical exercise and weight loss.…”

“…[19][20][21][22][23][24] In a previous study, we demonstrated that regular transient limb ischemia (RTLI), induced by six cycles of 5-min ischemia and 5-min reperfusion of the hind limb, implemented daily for 12 weeks could prevent atherosclerosis in hypercholesterolemic rabbits. 25 However, the mechanism by which RTLI protects against atherosclerosis remains unknown. We hypothesized that RTLI could protect endothelial function against the damage induced by hypercholesterolemia.…”