The Effects of Acarbose Treatment on Intimal Hyperplasia in a Rat Carotid Endarterectomy Model of Diet-Induced Insulin Resistance

Platelets are deposited on the exposed media following carotid endarterectomy and will continue to accumulate until neointima covers this thrombogenic surface. Radiolabelled platelet uptake was measured to assess the time to intimal repair.Autologous llllndium labelled platelets were infused 2 days and 2 months postoperatively in 10 patients undergoing unilateral carotid endarterectomy. Platelet accumulation was measured daily by gamma camera images counting radioactivity over the operated artery and comparing it to the contralateral side as Carotid Uptake Ratio (CUR).Mean (±sem) counts per gamma camera cell over the operated side at 24 hours were 46.3± 4.3 compared to 38.6± 3.9 on the unoperated side (p<0.001). At 2 months this difference had disappeared with counts of 38.8± 3.2 and 39.1± 3.2 over the operated and reference arteries respectively. Early postoperative CUR at 1.22± 0.04 was significantly higher than 1.01± 0.06 at 2 months which equates to no radiolabelled platelet uptake (p< 0.01). Radioiabellea platelet uptake was visible on 8 of the 10 early scans, but this was seen in only 2 patients at 2 months, both of whom had a persistently high CUR indicating continued platelet accumulation at that time.Early postoperative platelet deposition decreases in the weeks following carotid endarterectomy presumably due to the development of a neointima. Those cases with persistently high platelet accumulation may have luminal thrombus which could lead intimal hyperplasia and restenosis.

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Animal models of catheter-induced intimal hyperplasia in type 1 and type 2 diabetes and the effects of pharmacologic intervention

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y08-098 ◽

2009 ◽

Vol 87 (1) ◽

pp. 37-50 ◽

Cited By ~ 8

Author(s):

D.B. McNamara ◽

S.N. Murthy ◽

A.N. Fonseca ◽

C.V. Desouza ◽

P.J. Kadowitz ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Animal Models ◽

Vascular Injury ◽

Intimal Hyperplasia ◽

In Vivo Studies ◽

Impaired Insulin

Diabetes is a complex disorder characterized by impaired insulin formation, release or action (insulin resistance), elevated blood glucose, and multiple long-term complications. It is a common endocrine disorder of humans and is associated with abnormalities of carbohydrate and lipid metabolism. There are two forms of diabetes, classified as type 1 and type 2. In type 1 diabetes, hyperglycemia is due to an absolute lack of insulin, whereas in type 2 diabetes, hyperglycemia is due to a relative lack of insulin and insulin resistance. More than 90% of people with diabetes have type 2 with varied degrees of insulin resistance. Insulin resistance is often associated with impaired insulin secretion, and hyperglycemia is a common feature in both types of diabetes, but failure to make a distinction between the types of diabetes in different animal models has led to confusion in the literature. This is particularly true in relation to cardiovascular disease in the presence of diabetes and especially the response to vascular injury, in which there are major differences between the two types of diabetes. Animal models do not completely mimic the clinical disease seen in humans. Animal models are at best analogies of the pathologic process they are designed to represent. The focus of this review is an analysis of intimal hyperplasia following catheter-induced vascular injury, including factors that may complicate comparisons between different animal models or between in vitro and in vivo studies. We examine the variables, pitfalls, and caveats that follow from the manner of induction of the injury and the diabetic state of the animal. The efficacy of selected antidiabetic drugs in inhibiting the development of the hyperplastic response is also discussed.

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Homozygous receptors for insulin and not IGF-1 accelerate intimal hyperplasia in insulin resistance and diabetes

Nature Communications ◽

10.1038/s41467-019-12368-2 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Qian Li ◽

Jialin Fu ◽

Yu Xia ◽

Weier Qi ◽

Atsushi Ishikado ◽

...

Keyword(s):

Insulin Resistance ◽

Smooth Muscle ◽

Vascular Smooth Muscle Cells ◽

Insulin Signaling ◽

Intimal Hyperplasia ◽

Insulin Binding ◽

Extracellular Domain ◽

Rna Seq ◽

Intracellular Domain ◽

Arterial Intima

Abstract Insulin and IGF-1 actions in vascular smooth muscle cells (VSMC) are associated with accelerated arterial intima hyperplasia and restenosis after angioplasty, especially in diabetes. To distinguish their relative roles, we delete insulin receptor (SMIRKO) or IGF-1 receptor (SMIGF1RKO) in VSMC and in mice. Here we report that intima hyperplasia is attenuated in SMIRKO mice, but not in SMIGF1RKO mice. In VSMC, deleting IGF1R increases homodimers of IR, enhances insulin binding, stimulates p-Akt and proliferation, but deleting IR decreases responses to insulin and IGF-1. Studies using chimeras of IR(extracellular domain)/IGF1R(intracellular-domain) or IGF1R(extracellular domain)/IR(intracellular-domain) demonstrate homodimer IRα enhances insulin binding and signaling which is inhibited by IGF1Rα. RNA-seq identifies hyaluronan synthase2 as a target of homo-IR, with its expression increases by IR activation in SMIGF1RKO mice and decreases in SMIRKO mice. Enhanced intima hyperplasia in diabetes is mainly due to insulin signaling via homo-IR, associated with increased Has2 expression.

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Increased Intimal Hyperplasia After Carotid Endarterectomy in Spontaneously Hypertensive Rats

Vascular Surgery ◽

10.1177/153857440103500103 ◽

2001 ◽

Vol 35 (1) ◽

pp. 11-18 ◽

Cited By ~ 5

Author(s):

John Charles Drouilhet ◽

Fred Southern ◽

D. Keith Williams ◽

Aliza T. Brown ◽

John Eidt ◽

...

Keyword(s):

Carotid Endarterectomy ◽

Intimal Hyperplasia ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive

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Effect of Clopidogrel on Platelet Aggregation and Intimal Hyperplasia following Carotid Endarterectomy in the Rat

Vascular ◽

10.1258/rsmvasc.13.1.43 ◽

2005 ◽

Vol 13 (1) ◽

pp. 43-49 ◽

Cited By ~ 10

Author(s):

Shelly L. Bledsoe ◽

Aliza T. Brown ◽

Joseph A. Davis ◽

Hongjiang Chen ◽

John F. Eidt ◽

...

Keyword(s):

Platelet Aggregation ◽

Carotid Endarterectomy ◽

Intimal Hyperplasia ◽

Antiplatelet Agent ◽

Plasma Homocysteine ◽

Significant Morbidity ◽

Sprague Dawley ◽

Platelet Activity ◽

Vascular Intervention ◽

Sprague Dawley Rats

Intimal hyperplasia results in significant morbidity and mortality following vascular intervention. Both platelets and elevated homocysteine have been implicated in the development of intimal hyperplasia. We previously demonstrated that a locally applied antiplatelet agent decreases the development of intimal hyperplasia. We were therefore interested in a systemic antiplatelet agent, clopidogrel. We hypothesized that clopidogrel would decrease platelet aggregation and activity and intimal hyperplasia. Male Sprague-Dawley rats underwent carotid endarterectomy (CEA) and treatment with either placebo or varying regimens of clopidogrel, including chronic, pre-CEA bolus, chronic plus pre-CEA bolus, and chronic plus post-CEA bolus; a homocystine diet was used to elevate both plasma homocysteine and the degree of intimal hyperplasia. Platelet aggregation, platelet activity, and intimal hyperplasia were then assessed. Platelet aggregation was not decreased with chronic clopidogrel; however, it was decreased with pre-CEA bolus clopidogrel. Similarly, platelet activity was not inhibited by chronic clopidogrel but was inhibited by pre-CEA and chronic plus pre-CEA bolus clopidogrel. Neither chronic, pre-CEA bolus, chronic plus pre-CEA bolus, nor chronic plus post-CEA bolus clopidogrel resulted in a decrease in intimal hyperplasia. Although pre-CEA bolus clopidogrel resulted in a decrease in both platelet aggregation and activity, it was unable to decrease the development of intimal hyperplasia at any dose. Additional factors must therefore contribute to the pathologic development of intimal hyperplasia.

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