Diastolic dysfunction in a pre-clinical model of diabetes is associated with changes in the cardiac non-myocyte cellular composition.
Diastolic dysfunction in a pre-clinical model of diabetes is associated with changes in the cardiac non-myocyte cellular composition.
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DOI：
10.1186/s12933-021-01303-9
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发表时间：
2021-06-01
影响因子：
9.3
通讯作者：
Ritchie RH
中科院分区：
文献类型：
--
作者：
Cohen CD;De Blasio MJ;Lee MKS;Farrugia GE;Prakoso D;Krstevski C;Deo M;Donner DG;Kiriazis H;Flynn MC;Gaynor TL;Murphy AJ;Drummond GR;Pinto AR;Ritchie RH
糖尿病与心血管疾病的风险显著升高相关，其具体病理生理机制尚不清楚。最近的研究改变了我们对心脏细胞结构的理解，糖尿病伴随的细胞变化尚未详细研究。本研究旨在观察小鼠糖尿病心脏细胞景观的变化，以确定糖尿病心脏中潜在的细胞主角。在雄性FVB/N小鼠中通过低剂量链脲佐菌素和高脂肪饮食诱导糖尿病26周。在终点时通过超声心动图测量心脏功能。在终点时对来自非糖尿病小鼠和糖尿病小鼠的心室以及血液、脾脏和骨髓进行流式细胞术。为了验证流式细胞术结果，对年龄匹配的小鼠的左心室进行免疫荧光染色。糖尿病小鼠在终点时表现出高血糖和糖耐量受损。超声心动图显示糖尿病小鼠的E：A和e '：a'比率降低，表明舒张功能障碍。实验组之间的收缩功能没有差异。对心脏细胞结构的详细检查发现，由于心脏成纤维细胞的显著增加，糖尿病导致常驻间充质细胞（RMCs）升高，而平滑肌细胞的比例减少。此外，我们发现心脏和血液中Ly 6Chi单核细胞的水平增加。与此相一致，糖尿病小鼠骨髓造血干细胞的比例增加。小鼠糖尿病导致心脏细胞结构的明显变化。这些变化，特别是成纤维细胞水平的增加，为理解糖尿病中心脏细胞结构的变化提供了一个框架。结果还指出了在这种情况下新的细胞机制，这可能进一步有助于药物治疗的发展，以减轻糖尿病相关心肌病的进展。在线版本包含补充材料，可通过10.1186/s12933-021-01303-9获得。
Diabetes is associated with a significantly elevated risk of cardiovascular disease and its specific pathophysiology remains unclear. Recent studies have changed our understanding of cardiac cellularity, with cellular changes accompanying diabetes yet to be examined in detail. This study aims to characterise the changes in the cardiac cellular landscape in murine diabetes to identify potential cellular protagonists in the diabetic heart. Diabetes was induced in male FVB/N mice by low-dose streptozotocin and a high-fat diet for 26-weeks. Cardiac function was measured by echocardiography at endpoint. Flow cytometry was performed on cardiac ventricles as well as blood, spleen, and bone-marrow at endpoint from non-diabetic and diabetic mice. To validate flow cytometry results, immunofluorescence staining was conducted on left-ventricles of age-matched mice. Mice with diabetes exhibited hyperglycaemia and impaired glucose tolerance at endpoint. Echocardiography revealed reduced E:A and e’:a’ ratios in diabetic mice indicating diastolic dysfunction. Systolic function was not different between the experimental groups. Detailed examination of cardiac cellularity found resident mesenchymal cells (RMCs) were elevated as a result of diabetes, due to a marked increase in cardiac fibroblasts, while smooth muscle cells were reduced in proportion. Moreover, we found increased levels of Ly6Chi monocytes in both the heart and in the blood. Consistent with this, the proportion of bone-marrow haematopoietic stem cells were increased in diabetic mice. Murine diabetes results in distinct changes in cardiac cellularity. These changes—in particular increased levels of fibroblasts—offer a framework for understanding how cardiac cellularity changes in diabetes. The results also point to new cellular mechanisms in this context, which may further aid in development of pharmacotherapies to allay the progression of cardiomyopathy associated with diabetes. The online version contains supplementary material available at 10.1186/s12933-021-01303-9.
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影响因子：
20.1
作者：
Pinto AR;Ilinykh A;Ivey MJ;Kuwabara JT;D'Antoni ML;Debuque R;Chandran A;Wang L;Arora K;Rosenthal NA;Tallquist MD
通讯作者：
Tallquist MD
影响因子：
6.1
作者：
Fowlkes, Vennece;Clark, Jessica;Fix, Charity;Law, Brittany A.;Morales, Mary O.;Qiao, Xian;Ako-Asare, Kayla;Goldsmith, Jack G.;Carver, Wayne;Murray, David B.;Goldsmith, Edie C.
通讯作者：
Goldsmith, Edie C.
影响因子：
9.3
作者：
Baron M;Veres A;Wolock SL;Faust AL;Gaujoux R;Vetere A;Ryu JH;Wagner BK;Shen-Orr SS;Klein AM;Melton DA;Yanai I
通讯作者：
Yanai I
影响因子：
64.8
作者：
Litviňuková M;Talavera-López C;Maatz H;Reichart D;Worth CL;Lindberg EL;Kanda M;Polanski K;Heinig M;Lee M;Nadelmann ER;Roberts K;Tuck L;Fasouli ES;DeLaughter DM;McDonough B;Wakimoto H;Gorham JM;Samari S;Mahbubani KT;Saeb-Parsy K;Patone G;Boyle JJ;Zhang H;Zhang H;Viveiros A;Oudit GY;Bayraktar OA;Seidman JG;Seidman CE;Noseda M;Hubner N;Teichmann SA
通讯作者：
Teichmann SA
影响因子：
29
作者：
Nagareddy PR;Kraakman M;Masters SL;Stirzaker RA;Gorman DJ;Grant RW;Dragoljevic D;Hong ES;Abdel-Latif A;Smyth SS;Choi SH;Korner J;Bornfeldt KE;Fisher EA;Dixit VD;Tall AR;Goldberg IJ;Murphy AJ
通讯作者：
Murphy AJ