MRI-based in vivo detection of coronary microvascular dysfunction before alterations in cardiac function induced by short-term high-fat diet in mice.
MRI-based in vivo detection of coronary microvascular dysfunction before alterations in cardiac function induced by short-term high-fat diet in mice.
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DOI：
10.1038/s41598-021-98401-1
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发表时间：
2021-09-23
影响因子：
4.6
通讯作者：
Chłopicki S
中科院分区：
文献类型：
--
作者：
Kwiatkowski G;Bar A;Jasztal A;Chłopicki S
内皮功能障碍是代谢性疾病中血管异常的标志之一，并且在喂食高脂饮食（HFD）的小鼠的冠状动脉和外周循环中反复得到证实，特别是在长期HFD之后。然而，短期HFD喂养后冠状动脉微血管内皮功能障碍的发生与心脏舒张和收缩功能恶化之间的时间关系尚未研究。本研究旨在将小鼠短期饲喂 HFD 后冠状动脉微血管内皮功能与体内总体心脏性能指数的变化联系起来。短期饲喂 HFD（60% 脂肪 + 1% 胆固醇）会导致冠状动脉微血管功能严重受损，通过体内 MRI T1 映射评估的一氧化氮合酶抑制（L-NAME）效果减弱就证明了这一点。早在 HFD 治疗 7 天后就发现冠状动脉微血管功能恶化，并在 HFD 治疗 8 周后进一步下降。 HFD 引起的冠状微血管功能障碍与心肌毛细血管密度受损无关，并且在通过葡萄糖耐量试验评估的全身胰岛素抵抗之前就存在。使用 A2A 腺苷受体激动剂 regadenoson 评估的基础冠状动脉流量和冠状动脉储备在 HFD 喂养的小鼠中也没有改变。组织学分析未发现心肌细胞肥大或纤维化。早在 HFD 7 天后就检测到心肌细胞中脂质积累增加，并在 HFD 8 周后保持在相似水平。多参数心脏 MRI 显示心脏收缩功能下降，包括射血率下降、收缩末期容积增加和舒张期心肌应变下降，射血分数受损，但直到 HFD 4 周后才出现这种情况。短期高脂饮食喂养会导致冠状动脉微循环中的早期内皮功能障碍，然后导致心脏功能和全身胰岛素抵抗的改变。
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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影响因子：
3.5
作者：
Carbone, Salvatore;Mauro, Adolfo G.;Toldo, Stefano
通讯作者：
Toldo, Stefano
影响因子：
5.4
作者：
Bar, Anna;Targosz-Korecka, Marta;Chlopicki, Stefan
通讯作者：
Chlopicki, Stefan
影响因子：
2.9
作者：
Bar, Anna;Skorka, Tomasz;Chlopicki, Stefan
通讯作者：
Chlopicki, Stefan
影响因子：
37.8
作者：
Flammer AJ;Anderson T;Celermajer DS;Creager MA;Deanfield J;Ganz P;Hamburg NM;Lüscher TF;Shechter M;Taddei S;Vita JA;Lerman A
通讯作者：
Lerman A
DOI：
10.1186/1532-429x-15-109
发表时间：
2013-12-31
期刊：
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance
影响因子：
--
作者：
Kramer SP;Powell DK;Haggerty CM;Binkley CM;Mattingly AC;Cassis LA;Epstein FH;Fornwalt BK
通讯作者：
Fornwalt BK