Coronary Artery Responses to Physiological Stimuli Are Improved by Deferoxamine but not by
            <scp>l</scp>
            -Arginine in Non–Insulin-Dependent Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Risk Factors

Nitenberg, A; Paycha, Frédéric; Ledoux, Séverine; Sachs, R. N.; Attali, Jean-Raymond; Valensi, P.

doi:10.1161/01.cir.97.8.736

Cited by 117 publications

(75 citation statements)

References 70 publications

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“…Thus, the endothelium facilitates vasodilation of both resistance and large coronary vessels (22,23). Conversely, CPT constricts atherosclerotic coronary arteries (9,24) as well as both coronary arteries and microcirculation in patients with risk factors but normal arteries (5,10,25,26). In this study, CPT induced constriction of epicardial coronary arteries in most diabetic patients, whereas the magnitude of dilation of the arteries of control subjects was comparable to that reported in other studies (9,24).…”

Section: Cpt Response As a Witness Of Coronary Endothelial Dysfunctionsupporting

confidence: 82%

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Prognostic Value of Epicardial Coronary Artery Constriction to the Cold Pressor Test in Type 2 Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Major Coronary Risk Factors

et al. 2004

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OBJECTIVE -Endothelium-dependent coronary dilation is impaired in diabetic patients and has been found to independently predict cardiovascular events (CVEs) in patients with multiple coronary risk factors. The aim of this study was to evaluate the outcome of type 2 diabetic patients on the basis of epicardial coronary dysfunction.RESEARCH DESIGN AND METHODS -We examined 56 control subjects (aged 51.7 Ϯ 6.4 years) using coronary artery response to the cold pressor test (quantitative coronary angiography) and compared them with 72 type 2 diabetic patients (aged 50.3 Ϯ 8.5 years) without other major coronary risk factors.RESULTS -Average diameter change was 17.2 Ϯ 10.4% in the control subjects, dilation occurred in 91.1% of subjects, no change occurred in 8.9%, and there was no constriction. Average diameter change was Ϫ14.4 Ϯ 12.1% in diabetic patients (P Ͻ 0.001 vs. control subjects), constriction occurred in 73.6%, no change occurred in 26.4%, and there was no dilation. CVEs were recorded with a mean follow-up of 45 Ϯ 19 months. There was 1 CVE in the control group and 26 CVEs in 18 of 72 diabetic patients (P Ͻ 0.001 vs. control subjects), with 23 events in 16 of 53 diabetic patients with coronary artery constriction (P Ͻ 0.001 vs. control subjects), and 3 events in 2 of 19 diabetic patients with no diameter change (NS vs. control subjects).CONCLUSIONS -In type 2 diabetic patients without other major coronary risk factors, constriction of angiographically normal coronary arteries to the cold pressor test is predictive of long-term CVEs. Diabetes Care 27:208 -215, 2004I n diabetic patients, coronary atherosclerosis develops earlier than in other subjects and accounts for excessive morbidity and mortality (1). Because it is well established that the endothelium plays a key role in the regulation of vascular tone and the development of atherosclerosis (2), it has been suggested that endothelial dysfunction could be a predictor of cardiovascular risk (3). It has been shown that endothelium-dependent epicardial coronary artery vasodilation in response to acetylcholine (4) or physiological stimuli (5) is impaired in diabetic patients, suggesting that endothelial dysfunction occurs before the development of overt atherosclerosis. Recently, coronary endothelial dysfunction, evidenced by intracoronary acetylcholine, has been demonstrated to be an independent predictor of cardiovascular events (CVEs) in patients with coronary artery disease (6 -8) and patients with coronary risk factors (8). The cold pressor test (CPT), which activates the sympathetic nervous system, induces dilation of coronary arteries in control subjects and constriction of atherosclerotic coronary arteries (6,9,10). In diabetic patients, CPT has been shown to induce coronary artery constriction (5), which may reflect endothelial dysfunction.The purpose of the present study was to evaluate the ability of the epicardial coronary response to the CPT to predict CVEs in type 2 diabetic patients with angiographically normal coronary arteries and no other ma...

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Section: Cpt Response As a Witness Of Coronary Endothelial Dysfunctionsupporting

confidence: 82%

“…The cold pressor test (CPT), which activates the sympathetic nervous system, induces dilation of coronary arteries in control subjects and constriction of atherosclerotic coronary arteries (6,9,10). In diabetic patients, CPT has been shown to induce coronary artery constriction (5), which may reflect endothelial dysfunction.…”

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Prognostic Value of Epicardial Coronary Artery Constriction to the Cold Pressor Test in Type 2 Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Major Coronary Risk Factors

et al. 2004

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“…The cold pressor test, which activates the sympathetic nervous system, induces dilation of coronary arteries in normal subjects and constriction of atherosclerotic coronary arteries. 22,23 In diabetic patients, the cold pressure test has been shown to induce coronary artery constriction, 24 which may reflect endothelial dysfunction. Increased myocardial metabolism leads to an enhanced dilation and flow of epicardial coronary arteries, which is mainly determined by endothelium-derived nitric oxide.…”

Section: Discussionmentioning

confidence: 99%

Abnormal myocardial perfusion and contractile recruitment during exercise in type 1 diabetic patients

et al. 2005

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SummaryBackground: No data are available on the relationship between myocardial perfusion and left ventricular (LV) function in type 1 diabetes mellitus (T1DM), which may constitute a factor explaining the progressive contractile dysfunction to the overt phase of diabetic cardiomyopathy.Hypothesis: This study was undertaken to test whether myocardial perfusion abnormalities are present at rest and during exercise and whether they are related to contractile dysfunction in T1DM.Methods: Twenty-two patients with T1DM, aged 32 ± 8.3 years, without macro-or microvascular complications, and 10 controls, aged 31 ± 3 years, were studied. Left ventricular function and myocardial perfusion were assessed by two-dimensional and myocardial contrast echocardiography at rest and during handgrip (HG).Results: Fourteen patients with T1DM showed a decline in LV ejection fraction (LVEF) during HG (Group 1) while 8 had a normal response (Group 2). Both basal myocardial blood volume (MBV) and velocity (␤) were normal in T1DM. During exercise, MBV and ␤ increased and were associated with

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“…More specifically, individuals with diabetes display dysfunctions in the regulation of blood flow in coronary arterioles (2,3). Importantly, impairments in the appropriate vasodilatory response of myocardial arterioles to various pharmaceutical and physical stimuli can be present even if there is no discernible atherosclerotic blockage in these blood vessels (4,5). Moreover, increased flow-mediated dilation (FMD) in coronary arterioles is an important regulatory mechanism for controlling arteriolar diameter and blood flow in response to changes in wall shear stress, and this mechanism is also impaired in conditions of glucose dysregulation (6,7).…”

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confidence: 99%

“…Finally, the association of the disruption of caveolae assembly with uncoupling of eNOS in the diabetic group was convincingly demonstrated using isolated coronary arterioles from Cav-1 knockout mice, in which endothelial caveolae are completely absent. Importantly, the marked defects in FMD in response to wall shear stress were reversed by the addition of sepiapterin, a stable precursor of the NOS cofactor BH 4 , in an NO-dependent fashion. Overall, these impairments in vasomotor regulation of coronary arterioles and FMD in diabetes likely contribute to an overall increase in the risk of coronary microvascular disease.…”

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confidence: 99%

A Radical Concept on Caveolae and Endothelial Dysfunction in Coronary Microvascular Disease in Diabetes

Henriksen

2014

Diabetes

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The risk of cardiovascular disease is markedly elevated in individuals with diabetes, representing the primary cause of morbidity and mortality in these diabetic patients (1). More specifically, individuals with diabetes display dysfunctions in the regulation of blood flow in coronary arterioles (2,3). Importantly, impairments in the appropriate vasodilatory response of myocardial arterioles to various pharmaceutical and physical stimuli can be present even if there is no discernible atherosclerotic blockage in these blood vessels (4,5). Moreover, increased flow-mediated dilation (FMD) in coronary arterioles is an important regulatory mechanism for controlling arteriolar diameter and blood flow in response to changes in wall shear stress, and this mechanism is also impaired in conditions of glucose dysregulation (6,7).While the underlying etiology for the dysfunctions in the coronary microcirculation in diabetes is certainly multifactorial, the contribution of impairments in the endothelial nitric oxide (NO)-generating system and their association with the excess generation of reactive oxygen species (ROS) appears to be crucial in the development of these vascular abnormalities. For example, the impairment of the induction of vasodilation in coronary arterioles in the db/db mouse, a model of obesity-associated insulin resistance and type 2 diabetes, is related to limitations in NO availability (8,9). It is of great interest that NO availability can be compromised by interactions with superoxide anion, with a by-product of this reaction being the generation of peroxynitrite (OONO 2 ), an ROS that itself is known to mediate deleterious effects on the cardiovascular system in diabetes (10). However, prior to the study of Cassuto et al. (11), which appears in this issue, the specific impact of OONO 2 on the endothelial caveolae, which is required for the proper functionality of endothelial NO synthase (eNOS) (12), and the subsequent effect of this interaction on NO-regulated FMD in response to changes in wall shear stress in conditions of human diabetes had not been rigorously addressed in the scientific literature.The study of Cassuto et al. (11) convincingly advances the concept that, in human diabetes, defects in the ability of NO to facilitate vasodilation in coronary arterioles under conditions of increased OONO 2 exposure are related to the impaired expression of the caveloin-1 (Cav-1), an important structural component of caveolae in the endothelial membrane. Using tissue isolated from older nondiabetic subjects and subjects with either type 1 or 2 diabetes, the authors demonstrated that in vitro increases in FMD due to enhanced wall shear stress were severely reduced in coronary arterioles from diabetic subjects compared with coronary arterioles from nondiabetic subjects. Moreover, these vasomotor defects were associated with augmented OONO 2 production, as reflected by 3-nitrotyrosine levels (a biomarker of OONO 2 -mediated protein nitration), and were reproduced by direct incubation of arterioles with OONO...

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Coronary Artery Responses to Physiological Stimuli Are Improved by Deferoxamine but not by l -Arginine in Non–Insulin-Dependent Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Risk Factors

Cited by 117 publications

References 70 publications

Prognostic Value of Epicardial Coronary Artery Constriction to the Cold Pressor Test in Type 2 Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Major Coronary Risk Factors

Prognostic Value of Epicardial Coronary Artery Constriction to the Cold Pressor Test in Type 2 Diabetic Patients With Angiographically Normal Coronary Arteries and No Other Major Coronary Risk Factors

Abnormal myocardial perfusion and contractile recruitment during exercise in type 1 diabetic patients

A Radical Concept on Caveolae and Endothelial Dysfunction in Coronary Microvascular Disease in Diabetes

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