Differential Biological Effects of Dietary Lipids and Irradiation on the Aorta, Aortic Valve, and the Mitral Valve.
Differential Biological Effects of Dietary Lipids and Irradiation on the Aorta, Aortic Valve, and the Mitral Valve.
复制标题
DOI：
10.3389/fcvm.2022.839720
复制
发表时间：
2022
影响因子：
3.6
通讯作者：
Oury C
中科院分区：
文献类型：
--
作者：
Donis N;Jiang Z;D'Emal C;Hulin A;Debuisson M;Dulgheru R;Nguyen ML;Postolache A;Lallemand F;Coucke P;Martinive P;Herzog M;Pamart D;Terrell J;Pincemail J;Drion P;Delvenne P;Nchimi A;Lancellotti P;Oury C
膳食胆固醇和棕榈酸是影响动脉和心脏瓣膜的心血管疾病 (CVD) 的危险因素。经常用作抗癌治疗的电离辐射会促进CVD。人们对这些不同疾病表现的具体病理生理学知之甚少。因此，我们在兔心血管疾病模型中研究了这些膳食脂质及其心脏辐射对动脉和心脏瓣膜的生物效应。富含胆固醇的饮食导致主动脉壁和主动脉瓣叶增厚，主动脉、二尖瓣和主动脉瓣免疫细胞浸润，以及主动脉瓣钙化。在二尖瓣和主动脉瓣中检测到大量表达α-平滑肌肌动蛋白的细胞。富含猪油的饮食引起大量主动脉和主动脉瓣钙化，但没有检测到免疫细胞浸润。与单独使用胆固醇相比，在胆固醇饮食中添加心脏照射会在粥样斑块和主动脉瓣中产生更多的钙化和更多的免疫细胞浸润。主动脉和心脏瓣膜的RNA测序（RNAseq）分析表明，富含胆固醇的饮食主要引发主动脉、主动脉和二尖瓣中与炎症相关的生物过程，而心脏照射进一步增强了这种过程。富含猪油的饮食分别影响主动脉和主动脉瓣的钙化和肌肉相关过程。中性粒细胞计数和血小板因子 4 和 ent-8-iso-15(S)-PGF2α 的全身水平被确定为胆固醇诱导的组织改变的早期生物标志物，而心脏照射导致循环核小体水平升高。膳食胆固醇、棕榈酸和心脏照射与富含胆固醇的饮食相结合，导致了明显的血管和瓣膜病变的发展以及循环生物标志物的变化。因此，我们的研究强调了与 CVD 常见危险因素相关的前所未有的特殊性。
Dietary cholesterol and palmitic acid are risk factors for cardiovascular diseases (CVDs) affecting the arteries and the heart valves. The ionizing radiation that is frequently used as an anticancer treatment promotes CVD. The specific pathophysiology of these distinct disease manifestations is poorly understood. We, therefore, studied the biological effects of these dietary lipids and their cardiac irradiation on the arteries and the heart valves in the rabbit models of CVD. Cholesterol-enriched diet led to the thickening of the aortic wall and the aortic valve leaflets, immune cell infiltration in the aorta, mitral and aortic valves, as well as aortic valve calcification. Numerous cells expressing α-smooth muscle actin were detected in both the mitral and aortic valves. Lard-enriched diet induced massive aorta and aortic valve calcification, with no detectable immune cell infiltration. The addition of cardiac irradiation to the cholesterol diet yielded more calcification and more immune cell infiltrates in the atheroma and the aortic valve than cholesterol alone. RNA sequencing (RNAseq) analyses of aorta and heart valves revealed that a cholesterol-enriched diet mainly triggered inflammation-related biological processes in the aorta, aortic and mitral valves, which was further enhanced by cardiac irradiation. Lard-enriched diet rather affected calcification- and muscle-related processes in the aorta and aortic valve, respectively. Neutrophil count and systemic levels of platelet factor 4 and ent-8-iso-15(S)-PGF2α were identified as early biomarkers of cholesterol-induced tissue alterations, while cardiac irradiation resulted in elevated levels of circulating nucleosomes. Dietary cholesterol, palmitic acid, and cardiac irradiation combined with a cholesterol-rich diet led to the development of distinct vascular and valvular lesions and changes in the circulating biomarkers. Hence, our study highlights unprecedented specificities related to common risk factors that underlie CVD.