MRI-based in vivo detection of coronary microvascular dysfunction before alterations in cardiac function induced by short-term high-fat diet in mice

Autor: Grzegorz Kwiatkowski, Anna Bar, Agnieszka Jasztal, Stefan Chłopicki
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-021-98401-1
Popis: Abstract Endothelial dysfunction is one of the hallmarks of vascular abnormalities in metabolic diseases and has been repeatedly demonstrated in coronary and peripheral circulation in mice fed high-fat diet (HFD), particularly after long-term HFD. However, the temporal relationship between development of coronary microvascular endothelial dysfunction and deterioration in diastolic and systolic cardiac function after short-term feeding with HFD has not yet been studied. This study aimed to correlate the changes in coronary microvascular endothelial function and global cardiac performance indices in vivo after short-term feeding with HFD in mice. Short-term feeding with a HFD (60% fat + 1% cholesterol) resulted in severely impaired coronary microvascular function, as evidenced by the diminished effect of nitric oxide synthase inhibition (by L-NAME) assessed using T1 mapping via in vivo MRI. Deterioration of coronary microvascular function was detected as early as after 7 days of HFD and further declined after 8 weeks on a HFD. HFD-induced coronary microvascular dysfunction was not associated with impaired myocardial capillary density and was present before systemic insulin resistance assessed by a glucose tolerance test. Basal coronary flow and coronary reserve, as assessed using the A2A adenosine receptor agonist regadenoson, were also not altered in HFD-fed mice. Histological analysis did not reveal cardiomyocyte hypertrophy or fibrosis. Increased lipid accumulation in cardiomyocytes was detected as early as after 7 days of HFD and remained at a similar level at 8 weeks on a HFD. Multiparametric cardiac MRI revealed a reduction in systolic heart function, including decreased ejection rate, increased end-systolic volume and decreased myocardial strain in diastole with impaired ejection fraction, but not until 4 weeks of HFD. Short-term feeding with HFD resulted in early endothelial dysfunction in coronary microcirculation that preceded alteration in cardiac function and systemic insulin resistance.
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