Activated Platelets from Diabetic Rats Cause Endothelial Dysfunction by Decreasing Akt/Endothelial NO Synthase Signaling Pathway

Abstract

Diabetes is associated with endothelial dysfunction and platelet activation, both of which may contribute to increased cardiovascular risk. The purpose of this study was to characterize circulating platelets in diabetes and clarify their effects on endothelial function. Male Wistar rats were injected with streptozotocin (STZ) to induce diabetes. Each experiment was performed by incubating carotid arterial rings with platelets (1.65×107 cells/mL; 30 min) isolated from STZ or control rats. Thereafter, the vascular function was characterized in isolated carotid arterial rings in organ bath chambers, and each expression and activation of enzymes involved in nitric oxide and oxidative stress levels were analyzed. Endothelium-dependent relaxation induced by acetylcholine was significantly attenuated in carotid arteries treated with platelets isolated from STZ rats. Similarly, treatment with platelets isolated from STZ rats significantly reduced ACh-induced Akt/endothelial NO synthase signaling/NO production and enhanced TXB2 (metabolite of TXA2), while CD61 (platelet marker) and CD62P (activated platelet marker) were increased in carotid arteries treated with platelets isolated from STZ rats. Furthermore, the platelets isolated from STZ rats decreased total eNOS protein and eNOS dimerization, and increased oxidative stress. These data provide direct evidence that circulating platelets isolated from diabetic rats cause dysfunction of the endothelium by decreasing NO production (via Akt/endothelial NO synthase signaling pathway) and increasing TXA2. Moreover, activated platelets disrupt the carotid artery by increasing oxidative stress.

Relaxation Induced by Atrial Natriuretic Peptide Is Impaired in Carotid but Not Renal Arteries from Spontaneously Hypertensive Rats Due to Reduced BK_Ca Channel Activity

“…[41][42][43][44] For the relaxation studies, renal and carotid arterial rings were precontracted with a submaximal concentration of PE (i.e., 1-3 µM). When the PE-induced contraction had reached a plateau, ACh (10 −9 -10 −5 M), ANP (10 −10 -10 −7 M), or SNP (10 −10 -10…”

Stimulation of nitric oxide production contributes to the antiplatelet and antithrombotic effect of new peptide pENW (pGlu-Asn-Trp)

“…The activation and aggregation of platelets play an essential role in the development of vascular occlusive thrombi and increased cardiovascular risks in diabetes [2][3][4]. Antiplatelet therapy has emerged as a primary target in the treatment of thrombotic disorders such as acute coronary syndromes [5,6].…”

“…Factors which contribute to the thrombotic response to injury include (dys)function and/or activation of vascular cells [14] as well as circulating coagulation factors and platelets [1,4]. Reduced endothelial function is strongly associated with decreased nitric oxide (NO) production [15], and endothelium-derived NO is essential in the maintenance of vascular homeostasis [16].…”

The Impact of Umbilical Blood Flow Regulation on Fetal Development Differs in Diabetic and Non-Diabetic Pregnancy

“…The fetus gets oxygen and nutrition via the umbilical vessels, thus blood flow in the vessel is essential for fetal development. Diabetes is well-known to influence endothelial function [9,10]. Thus, endothelial function and blood flow regulation might be different in diabetic and non-diabetic ladies.…”