Age Exacerbates Neointima Growth In Carotid Arteries Of Zucker Diabetic Fatty Rats
Main Article Content
Abstract
Background:
Diabetes is a pervasive disease that can affect all organs and tissues of the body. Hyperinsulinemia, hyperglycemia, dyslipidemia and advanced glycation end products are but a few of the anomalies of diabetes that impinge upon the vasculature and are causal agents for vascular inflammation and atherosclerosis. The purpose of this study was to determine the effects of age, obesity and hyperinsulinemia on carotid arteries after mechanical injury and compare the parameters of intima media thickness, lumen diameter and blood flow velocity between 8-week and 16-week, control (CON)(lean) and experiment (EXP)(fat) litter-mate male Zucker Diabetic Fatty rats.
Methods:
The injured carotid arteries of 8-week and 16-week old male Zucker Diabetic Fatty rats and their CON littermates were catheterized for endarterectomy at Charles River Laboratories. Rats were transported to our vivarium one week after endarterectomies were completed. Using ultrasound imaging, internal lumen diameter, dorsal and ventral walls, external artery diameter and blood flow velocity of the injured carotid arteries (injured) were compared to the same parameters in the non-injured carotid arteries (internal non-injured) within the same age group, between CON and EXP rats of the same age group and between 8-week and 16-week age groups. One week after receiving the rats, each rat was anesthetized for 30 minutes for ultrasound measurements using an isoflurane-oxygen solution. Ultrasound images were collected on injured catheterized and non-injured CON carotid arteries on days 14, 21, 42 and 62 post surgery.
Results:
As age progressed, there were significant differences in the injured carotid lumen and injured total diameter measurements between the 8- and 16-week cohorts over time in CON and EXP rats. We noted that the injured carotid arteries of the 8-week cohorts never improved, while the same parameters of the 16-week cohorts did exhibit recovery. Interestingly, the 8-week rats demonstrated no change of the injured lumen over time after damage, while the 16-week rats demonstrated increased lumenal space, indicating recovery. In contrast, there were no differences in the non-injured carotid lumens and total diameters of 8-week and 16-week CON and experiment (EXP) rats. There were no significant differences between the blood flow velocities of the injured carotid arteries of the 8-week and 16-week cohorts over time. However, compared to the 8-week cohort, the non-injured carotid velocity of the 16-week rats was significantly lower in both CON and EXP rats. There were no significant differences in injured carotid measurements when comparing CON to EXP rats within the same age group.
Article Details
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References
1 Narizhneva NV, Razorenova OV, Podrez EA, Chen J, Chandrasekharan UM, DiCorleto PE, Plow EF, Topol EJ and Byzova TV (2005) Thrombospondin-1 up-regulates expression of cell adhesion molecules and promotes monocyte binding to endothelium. Faseb J 19: 1158-1160.
2 Ginsberg HN (2000) Insulin resistance and cardiovascular disease. J Clin Invest 106: 453-458.
3 Montagnani M and Quon MJ (2000) Insulin action in vascular endothelium: potential mechanisms linking insulin resistance with hypertension. Diabetes Obes Metab 2: 285-292.
4 Keihani S, Hosseinpanah F, Barzin M, Serahati S, Doustmohamadian S and Azizi F (2015) Abdominal obesity phenotypes and risk of cardiovascular disease in a decade of follow-up: the Tehran Lipid and Glucose Study. Atherosclerosis 238: 256-263.
5 Leng XY, Chen XY, Chook P, Xiong L, Lin WH, Liu JY, Tomlinson B, Thomas GN, Lam TH, Lam KS, Cheung BM and Wong KS (2013) Association between metabolic syndrome and carotid atherosclerosis: a community-based study in Hong Kong. Metab Syndr Relat Disord 11: 109-114.
6 Ong KL, McClelland RL, Rye KA, Cheung BM, Post WS, Vaidya D, Criqui MH, Cushman M, Barter PJ and Allison MA (2014) The relationship between insulin resistance and vascular calcification in coronary arteries, and the thoracic and abdominal aorta: the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis 236: 257-262.
7 Hempe J, Elvert R, Schmidts HL, Kramer W and Herling AW (2012) Appropriateness of the Zucker Diabetic Fatty rat as a model for diabetic microvascular late complications. Lab Anim 46: 32-39.
8 Rask-Madsen C, Li Q, Freund B, Feather D, Abramov R, Wu IH, Chen K, Yamamoto-Hiraoka J, Goldenbogen J, Sotiropoulos KB, Clermont A, Geraldes P, Dall'Osso C, Wagers AJ, Huang PL, Rekhter M, Scalia R, Kahn CR and King GL (2010) Loss of insulin signaling in vascular endothelial cells accelevelocitys atherosclerosis in apolipoprotein E null mice. Cell Metab 11: 379-389.
9 Blankenberg S, Barbaux S and Tiret L (2003) Adhesion molecules and atherosclerosis. Atherosclerosis 170: 191-203.
10 Salazar MR, Carbajal HA, Espeche WG, Aizpurua M, Leiva Sisnieguez CE, Leiva Sisnieguez BC, Stavile RN, March CE and Reaven GM (2016) Insulin resistance: The linchpin between prediabetes and cardiovascular disease. Diab Vasc Dis Res 13: 157-163.
11 Faienza MF, Acquafredda A, Tesse R, Luce V, Ventura A, Maggialetti N, Monteduro M, Giordano P and Cavallo L (2013) Risk factors for subclinical atherosclerosis in diabetic and obese children. Int J Med Sci 10: 338-343.
12 Sirbu A, Nicolae H, Martin S, Barbu C, Copaescu C, Florea S, Panela C and Fica S (2016) IGF-1 and Insulin Resistance Are Major Determinants of Common Carotid Artery Thickness in Morbidly Obese Young Patients. Angiology 67: 259-265.
13 Wasniewska M, Valenzise M, Manganaro A, Bombaci S, Iudicello R, Aversa T, De Luca F and Lombardo F (2011) Increased intima media thickness at many arterial sites in obese adolescents with abdominal adiposity, insulin resistance, and high LDL-cholesterol. J Endocrinol Invest 34: 647-649.
14 Leite A, Santos A, Monteiro M, Gomes L, Veloso M and Costa M (2012) Impact of overweight and obesity in carotid intima-media thickness of portuguese adolescents. Acta Paediatr 101: e115-121.
15 Slyper AH, Rosenberg H, Kabra A, Weiss MJ, Blech B, Gensler S and Matsumura M (2014) Early atherogenesis and visceral EXP in obese adolescents. Int J Obes (Lond) 38: 954-958.
16 Kotb NA, Gaber R, Salama M, Nagy HM and Elhendy A (2012) Clinical and biochemical predictors of increased carotid intima-media thickness in overweight and obese adolescents with type 2 diabetes. Diab Vasc Dis Res 9: 35-41.