Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia

Kaufmann, Philipp A.; Gnecchi‐Ruscone, Tomaso; Schäfers, Klaus P.; Lüscher, Thomas F.; Camici, Paolo G.

doi:10.1016/s0735-1097(00)00697-5

Cited by 185 publications

(110 citation statements)

References 64 publications

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“…The great interest for this issue, originated from previous clinical evidence that endothelial-dependent vasodilation as well as pharmacological (adenosine mediated) and metabolic coronary reserve of atherosclerotic-free or non flow-limiting atherosclerotic vessels at angiography, was reduced in hypercholesterolemic patients [12] [13] and could be normalized with the use of cholesterol-lowering strategies or NO donors [14]- [19]. Although a different contribution of total, LDL and HDL cholesterol to the impairment of coronary reserve was evidenced from previous experimental studies, they demonstrated an inhibitory effect of oxidized LDL and a protective role of HDL only on endothelium-dependent arterial vasodilation [20], concordant with clinical observations [21] [22]. On the other hand, the interplay between LDL and HDL and the association with other circulatory factors (cytokines, cell adhesion molecules) in coronary microvascular dysfunction are still partly unexplored.…”

Section: Introductionsupporting

confidence: 75%

HDL-Mediated Protection of Coronary Vasodilator Response to Adenosine in the Hypercholesterolemic Swine

Vozzi¹,

Pelosi²,

Puntoni³

et al. 2014

OJMIP

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Section: Introductionsupporting

confidence: 75%

HDL-Mediated Protection of Coronary Vasodilator Response to Adenosine in the Hypercholesterolemic Swine

Vozzi¹,

Pelosi²,

Puntoni³

et al. 2014

OJMIP

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“…In diabetes, endothelial dysfunction is considered as a critical and initiating factor in the development of chronic diabetic macro-and microvascular disease and it becomes a great challenge to understand its mechanisms and aetiology [43]. Most of the studies had focused on hyperglycaemia as the main cause of this impaired vascular function but compelling evidence in healthy [44], hypercholesterolaemic [45,46] and diabetic patients [47] suggests that LDL cholesterol concentration could also be a major cause of alteration of the endothelial function. However, in diabetic patients, impairment of endothelial function occurs even under normocholesterolaemic conditions with a normal LDL concentration [48] and intensive lipid lowering therapy by statins failed to improve vascular reactivity in several studies [49].…”

Section: Discussionmentioning

confidence: 99%

Effect of glycated LDL on microvascular tone in mice: a comparative study with LDL modified in vitro or isolated from diabetic patients

Nivoit

Wiernsperger

Moulin³

et al. 2003

Diabetologia

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Aims/hypothesis. In vitro studies have suggested that glycation of LDL might be implicated in diabetic microangiopathy. We therefore investigated the in vivo effects of LDL glycated in vitro on the mouse skeletal muscle arteriolar tone. Since glycation naturally occurs during diabetes, we also tested the effects of LDL isolated from diabetic patients. Methods. In anaesthetized mice, the spinotrapezius muscle microcirculation was observed, in situ, using the orthogonal polarization spectral imaging technology. The diameter of terminal (<20 µm) and small arterioles (20-40 µm) was measured before and after a bolus intravenous injection of glycated LDL followed by a continuous perfusion (115 µg/kg/min). Results. A slight decrease of terminal and small arterioles diameter (<10%) was observed with native LDL and LDL isolated from healthy subjects. In contrast, mildly glycated LDL induced a clear vasoconstriction of arterioles (>15%), which was further increased when highly glycated LDL was perfused (>22%). LDL isolated from diabetic patients mimicked the vasoconstriction obtained with in vitro mildly glycated LDL, which underwent similar glycation as those isolated from diabetic patients. Conclusion/Interpretation. Our results show in vivo that acute perfusion of both types of glycated LDL (artificially or naturally modified), cause major microvascular modification by enhancing arteriolar tone in skeletal muscle. These findings highlight a new role of glycated LDL at the level of microvessels. We suggest that glycation of LDL could contribute to the impaired vascular reactivity observed in diabetes. [Diabetologia (2003[Diabetologia ( ) 46:1550[Diabetologia ( -1558

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“…Through the years, several reports using PET have demonstrated microvascular dysfunction in narrowly selected subsets of patients with specific cardiovascular risk factors such as smoking [23], dyslipidemia [24], hypertension [25], diabetes mellitus [26] and rheumatic diseases [27].…”

Section: Microvascular Disease and Treatment Monitoringmentioning

confidence: 99%

PET myocardial perfusion quantification: anatomy of a spreading functional technique

Juárez-Orozco

Cruz-Mendoza

Guinto-Nishimura

et al. 2018

Clin Transl Imaging

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Purpose To summarize the physical principles, imaging method, available tools for and the clinical value of quantitative perfusion evaluation with cardiac PET as well as future aims in the field in a narrative review. Results Cardiac positron-emission tomography (PET) currently constitutes the reference standard for non-invasive quantitative evaluation of myocardial blood flow. This added modality provides useful information beyond standard semi-quantitative myocardial perfusion evaluation. A description of how the different phases of PET studies are interpreted is provided, as well as a short depiction of the most commonly used radiotracers and the main characteristics affecting their clinical utility. The diagnostic and prognostic utility concerning myocardial perfusion quantified in absolute terms is discussed and the additional contribution of the increasingly spread hybrid equipment is summarized. Conclusion PET myocardial perfusion represents an excellent noninvasive technique for the evaluation of known or suspected ischemic heart disease, and its clinical application should widen in the near future. The clinical value of PET quantitative perfusion is expected to improve patient outcomes and optimize therapeutic decisions, which constitute key elements for the future of cardiovascular medicine.

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Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia

Abstract: Low density lipoprotein cholesterol but not TC correlated inversely with CFR in hypercholesterolemic subjects. Thus, LDL-induced coronary microvascular dysfunction could play an important role in the pathogenesis of coronary artery disease and its complications.

Cited by 185 publications

References 64 publications

HDL-Mediated Protection of Coronary Vasodilator Response to Adenosine in the Hypercholesterolemic Swine

HDL-Mediated Protection of Coronary Vasodilator Response to Adenosine in the Hypercholesterolemic Swine

Effect of glycated LDL on microvascular tone in mice: a comparative study with LDL modified in vitro or isolated from diabetic patients

PET myocardial perfusion quantification: anatomy of a spreading functional technique

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