Obesity Is Associated with Lower Coronary Microvascular Density

Campbell, Duncan J.; Somaratne, J.; Prior, David; Yii, Michael; Kenny, James F.; Newcomb, Andrew; Kelly, Darren J.; Black, M. Jane

doi:10.1371/journal.pone.0081798

Cited by 46 publications

(41 citation statements)

References 46 publications

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“…Impaired HIF signalling would down‐regulate angiogenesis, ultimately resulting in reduced capillary density in the heart. Recently, histological analysis of non‐ischaemic myocardium from patients undergoing coronary artery bypass surgery showed that obesity was associated with lower coronary microvascular density . A previous study from our lab showed that overexpression of angiopoietin 1 improved capillary density in ischaemia‐induced obese db/db mouse hearts via up‐regulating HIF‐1α expression .…”

Section: Discussionmentioning

confidence: 91%

High‐fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT3 loss

Zeng

Vaka

et al. 2015

J Cellular Molecular Medi

111

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Mitochondrial dysfunction plays an important role in obesity-induced cardiac impairment. SIRT3 is a mitochondrial protein associated with increased human life span and metabolism. This study investigated the functional role of SIRT3 in obesity-induced cardiac dysfunction. Wild-type (WT) and SIRT3 knockout (KO) mice were fed a normal diet (ND) or high-fat diet (HFD) for 16 weeks. Body weight, fasting glucose levels, reactive oxygen species (ROS) levels, myocardial capillary density, cardiac function and expression of hypoxia-inducible factor (HIF)-1α/-2α were assessed. HFD resulted in a significant reduction in SIRT3 expression in the heart. Both HFD and SIRT3 KO mice showed increased ROS formation, impaired HIF signalling and reduced capillary density in the heart. HFD induced cardiac hypertrophy and impaired cardiac function. SIRT3 KO mice fed HFD showed greater ROS production and a further reduction in cardiac function compared to SIRT3 KO mice on ND. Thus, the adverse effects of HFD on cardiac function were not attributable to SIRT3 loss alone. However, HFD did not further reduce capillary density in SIRT3 KO hearts, implicating SIRT3 loss in HFD-induced capillary rarefaction. Our study demonstrates the importance of SIRT3 in preserving heart function and capillary density in the setting of obesity. Thus, SIRT3 may be a potential therapeutic target for obesity-induced heart failure.

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Section: Discussionmentioning

confidence: 91%

High‐fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT3 loss

Zeng

Vaka

et al. 2015

J Cellular Molecular Medi

111

View full text Add to dashboard Cite

show abstract

“…Patients with HFpEF had higher body mass index than controls, and the findings of Mohammed et al are in agreement with the reported association of obesity with reduced microvascular density and increased pulmonary capillary wedge pressure in patients with coronary artery disease undergoing coronary artery bypass graft surgery. 2 Moreover, the inverse association between coronary microvascular density and pulmonary capillary wedge pressure in these patients with coronary artery disease provides support for a role for reduced microvascular density in increased left ventricular filling pressures. 2 Mohammed et al discuss the possible contribution of microvascular destruction and insufficient angiogenesis to the lower microvascular density of HFpEF patients.…”

Section: To the Editormentioning

confidence: 91%

“…2 Moreover, the inverse association between coronary microvascular density and pulmonary capillary wedge pressure in these patients with coronary artery disease provides support for a role for reduced microvascular density in increased left ventricular filling pressures. 2 Mohammed et al discuss the possible contribution of microvascular destruction and insufficient angiogenesis to the lower microvascular density of HFpEF patients. However, they do not consider the role of cardiomyocyte size in determining microvascular density.…”

Section: To the Editormentioning

confidence: 91%

“…5 Increased cardiomyocyte size may also explain the lower microvascular density of obese individuals, as indicated by the similar diffusion radius/cardiomyocyte width ratio of obese and nonobese individuals. 2 Mohammed at al noted increased heart weight in HFpEF patients, and the diffusion radius/cardiomyocyte width ratio may help explain the extent to which cardiomyocyte hypertrophy contributes to the reduced coronary microvascular density of their HFpEF patients.…”

Section: To the Editormentioning

confidence: 98%

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Letter by Campbell Regarding Article, “Coronary Microvascular Rarefaction and Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction”

Campbell

2015

Circulation

Self Cite

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“…leptin, tumour necrosis factor‐α, interleukin‐1β and interleukin‐6), particularly from fat depots surrounding visceral organs . Acting in a paracrine manner, these adipocytokines can cause microcirculatory rarefaction and fibrosis of underlying organs, especially the heart and kidneys . Interestingly, chronic systemic inflammatory states other than obesity (e.g.…”

Section: Evolution Of Obesity‐related Heart Failure With Preserved Ejmentioning

confidence: 99%

The conundrum of patients with obesity, exercise intolerance, elevated ventricular filling pressures and a measured ejection fraction in the normal range

Packer

2018

European J of Heart Fail

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Patients with obesity, a reduced exercise capacity, increased cardiac filling pressures and a measured left ventricular ejection fraction in the normal range do not have a homogeneous disorder, but instead, exhibit one of three phenotypes. First, many obese people exhibit sodium retention, plasma volume expansion and cardiac enlargement, and some are likely to have heart failure that is related to hypervolaemia, even though cardiac index and circulating levels of natriuretic peptides are not meaningfully increased. Second, in some middle‐aged men and women (particularly those with minimal co‐morbidities), levels of natriuretic peptides increase markedly and can lower systemic vascular resistance, thus leading to high‐output heart failure (HOHF) and glomerular hyperfiltration. Third, older obese people, particularly women with multiple co‐morbidities, exhibit the syndrome of heart failure with a preserved ejection fraction (HFpEF). Despite degrees of plasma volume expansion similar to HOHF, these patients exhibit only modestly increased ventricular dimensions and circulating levels of natriuretic peptides (despite a high prevalence of atrial fibrillation), and glomerular function is characteristically impaired. A conceptual framework is proposed to distinguish among the three phenotypes seen in obese patients with exercise intolerance, increased ventricular filling pressures and a measured left ventricular ejection fraction in the normal range, since they may respond differently to therapeutic interventions. Efforts are needed to enhance the recognition of heart failure in obese people and to ensure that clinical trials that are designed to study patients with HFpEF actually enrol those who have the disease.

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Obesity Is Associated with Lower Coronary Microvascular Density

Cited by 46 publications

References 46 publications

High‐fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT3 loss

High‐fat diet induces cardiac remodelling and dysfunction: assessment of the role played by SIRT3 loss

Letter by Campbell Regarding Article, “Coronary Microvascular Rarefaction and Myocardial Fibrosis in Heart Failure With Preserved Ejection Fraction”

The conundrum of patients with obesity, exercise intolerance, elevated ventricular filling pressures and a measured ejection fraction in the normal range

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