Functional improvement precedes structural regression of atherosclerosis.

Benzuly, Keith H.; Padgett, Richard C.; Kaul, Sanjay; Piegors, Donald J.; Armstrong, Marc P.; Heistad, D D

doi:10.1161/01.cir.89.4.1810

Cited by 90 publications

(42 citation statements)

References 40 publications

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“…Notably, in our study, only KP was able to prevent the development of a blunted kidney vasodilatory reserve, which confers adjunctive beneficial effects in the protection of the kidney. Similar to what happens in the periphery, changes in renal endothelium-dependent dilation could precede structural changes (31,32).…”

Section: Subanalysis For Agementioning

confidence: 87%

l-Arginine-Induced Vasodilation of the Renal Vasculature Is Preserved in Uremic Type 1 Diabetic Patients After Kidney and Pancreas but not After Kidney-Alone Transplantation

et al. 2004

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OBJECTIVE -In uremic type 1 diabetic patients, kidney and pancreas transplantation (KP) and kidney-alone transplantation (KD) provide full restoration of normal renal function; however, only KP, i.e., curing diabetes, is expected to prevent endothelial damages. Our aim was to study L-arginine-induced vasodilation of the renal vasculature in uremic type 1 diabetic patients after KP or KD using magnetic resonance (MR). RESEARCH DESIGN AND METHODS-MR quantitative flow measurements were performed in 15 KP patients (mean age 39.0 Ϯ 1.7 years, 10 men and 5 women), in 11 KD patients (mean age 47.3 Ϯ 1.9 years, 7 men and 4 women), and in 8 nondiabetic kidney transplant patients (mean age 44.0 Ϯ 4.8 years, 7 men and 1 woman), who were used as control subjects, to measure renal blood flow and velocity and renal vascular resistance before and immediately after infusion of L-arginine.RESULTS -Renal blood flow and velocity were not different at baseline in KP, KD, and control subjects. In contrast, during L-arginine administration renal blood flow increased significantly in KP subjects (basal 8.4 Ϯ 0.6 vs. post 9.6 Ϯ 0.8 ml/s, ⌬ 14.3 Ϯ 4.4%, P Ͻ 0.05) and in control subjects (basal 9.3 Ϯ 0.8 vs. post 9.1 Ϯ 0.8 ml/s, ⌬ 17.3 Ϯ 6.2%, P Ͻ 0.01), while it remained unchanged in KD subjects (basal 10.0 Ϯ 0.8 vs. post 11.6 Ϯ 0.9 ml/s, ⌬ Ϫ1.36 Ϯ 6.9%, NS). Parallel results have been achieved for renal blood velocity (KP subjects: 20.1 Ϯ 4.9%, P Ͻ 0.01; control subjects: 23.0 Ϯ 7.99%, P Ͻ 0.01; and KD subjects: Ϫ0.3 Ϯ 6.5%; NS). A reduction in renal vascular resistance in response to L-arginine was evident in KP and control subjects but not in KD patients. CONCLUSIONS -L-

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Section: Subanalysis For Agementioning

confidence: 87%

l-Arginine-Induced Vasodilation of the Renal Vasculature Is Preserved in Uremic Type 1 Diabetic Patients After Kidney and Pancreas but not After Kidney-Alone Transplantation

et al. 2004

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“…In addition to vascular tone, the endothelium regulates cell adhesion, platelet aggregation, coagulation, lipid transport and oxidation, inflammation, and mitogenesis (6). Changes in EDD precede structural changes during experimental induction or regression of atherosclerosis in monkeys (7). Endothelial function in patients who have undergone KP transplantation is normal; this could be the result of the reduction of the atherothrombotic state.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, endothelium modulates platelet adhesion, macrophage migration, lipid transport, and mitogenesis (6). Impairment of dilation ability is an important predictor of atherosclerosis and its complications (7). Diabetes, uremia, and hyperhomocystinemia are conditions with known increased proneness toward EDD (8).…”

mentioning

confidence: 99%

Effects of Kidney-Pancreas Transplantation on Atherosclerotic Risk Factors and Endothelial Function in Patients With Uremia and Type 1 Diabetes

Fiorina¹,

Rocca²,

Venturini³

et al. 2001

Diabetes

102

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“…In previous studies, we demonstrated that this diet produces both hyperhomocyst(e)inemia and hypercholesterolemia, with moderately severe atherosclerotic lesions in large vessels. 11,28 We anticipated that infusion of thrombin might generate higher levels of APC in atherosclerotic monkeys than in monkeys fed the control diet, because we previously observed increased protein C activation in explants of aorta and carotid artery from atherosclerotic monkeys. 11 In contrast to our expectations, however, levels of circulating APC were almost 20% lower after infusion of thrombin in atherosclerotic monkeys than in control monkeys.…”

Section: Lentz Et Al Impaired Anticoagulation In Atherosclerosismentioning

confidence: 99%

Impaired Anticoagulant Response to Infusion of Thrombin in Atherosclerotic Monkeys Associated With Acquired Defects in the Protein C System

Lentz

Fernández

Griffin

et al. 1999

ATVB

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Abstract-To examine the effects of atherosclerosis on the protein C anticoagulant pathway in vivo, we measured anticoagulant responses to intravenous administration of human ␣-thrombin or activated protein C (APC) in cynomolgus monkeys. Two groups of monkeys were fed either a control diet (nϭ18) or an atherogenic diet (nϭ12) that produces both hypercholesterolemia and moderate hyperhomocyst(e)inemia. A third group (nϭ8) was fed an atherogenic diet for 15 months, and then fed the atherogenic diet supplemented with B vitamins for 6 months to correct the hyperhomocyst(e)inemia. The plasma homocyst(e)ine level was higher in monkeys fed the atherogenic diet (9.6Ϯ1.0 mol/L) than in monkeys fed the control diet (3.7Ϯ0.2 mol/L) or the atherogenic diet with B vitamins (3.6Ϯ0.2 mol/L) (PϽ0.001). Infusion of thrombin produced a much greater prolongation of the activated partial thromboplastin time in monkeys fed the control diet (52Ϯ10 seconds) than in monkeys fed the atherogenic diet either with (24Ϯ4 seconds) or without (27Ϯ5 seconds) supplemental B vitamins (PϽ0.02). Thrombin-dependent generation of circulating APC was higher in control (294Ϯ17 U/mL) than in atherosclerotic (240Ϯ14 U/mL) monkeys (PϽ0.05), although levels of fibrinogen, plasminogen, D-dimer, and thrombin-antithrombin complexes were similar in each group. Injection of human APC produced a similar prolongation of the activated partial thromboplastin time in control (31Ϯ3 seconds) and atherosclerotic (29Ϯ2 seconds) monkeys. These findings provide evidence for impaired anticoagulation, due partly to decreased formation of APC, in atherosclerosis. Key Words: atherosclerosis Ⅲ cholesterol Ⅲ homocysteine Ⅲ protein C Ⅲ thrombomodulin T hrombin, a major regulator of hemostasis, has both procoagulant and anticoagulant properties. 1 Procoagulant effects of thrombin include proteolytic activation of factors V, VIII, and XI; cleavage of fibrinogen to form a fibrin clot; and stimulation of platelet aggregation. A major anticoagulant effect of thrombin involves activation of protein C, a vitamin K-dependent plasma anticoagulant. Thrombin's procoagulant and anticoagulant activities are regulated by thrombomodulin, a cofactor that is expressed on the luminal surface of vascular endothelium. 2 When bound to thrombomodulin, thrombin's ability to catalyze procoagulant reactions is inhibited, but its ability to activate protein C is enhanced Ͼ1000-fold. 3 The protein C anticoagulant pathway is impaired in patients with inherited deficiencies of protein C or protein S and also in patients with a mutation in factor V (factor V Leiden) that renders it resistant to activated protein C (APC). 4,5 The physiological importance of the protein C anticoagulant pathway is underscored by the observation that resistance to APC is found in 20% to 50% of patients with venous thromboembolism. 6 Resistance to APC that is independent of factor V Leiden may be associated with increased risk of stroke. 7,8 In a previous study, we observed impaired endotheliumdependent vasodilatation and decreas...

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Functional improvement precedes structural regression of atherosclerosis.

Cited by 90 publications

References 40 publications

l-Arginine-Induced Vasodilation of the Renal Vasculature Is Preserved in Uremic Type 1 Diabetic Patients After Kidney and Pancreas but not After Kidney-Alone Transplantation

l-Arginine-Induced Vasodilation of the Renal Vasculature Is Preserved in Uremic Type 1 Diabetic Patients After Kidney and Pancreas but not After Kidney-Alone Transplantation

Effects of Kidney-Pancreas Transplantation on Atherosclerotic Risk Factors and Endothelial Function in Patients With Uremia and Type 1 Diabetes

Impaired Anticoagulant Response to Infusion of Thrombin in Atherosclerotic Monkeys Associated With Acquired Defects in the Protein C System

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