Singh Pratibha, Sun Jiangming, Cavalera Michele, Al-Sharify Dania, Matthes Frank, Barghouth Mohammad, Tengryd Christoffer, Dunér Pontus, Persson Ana, Sundius Lena, Nitulescu Mihaela, Bengtsson Eva, Rattik Sara, Engelbertsen Daniel, Orho-Melander Marju, Nilsson Jan, Monaco Claudia, Goncalves Isabel, Edsfeldt Andreas
Cardiovascular Research-Translational Studies, Lund University, Malmö, Sweden.
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Nat Commun. 2024 Dec 9;15(1):10464. doi: 10.1038/s41467-024-50753-8.
Type 2 diabetes is associated with cardiovascular disease, possibly due to impaired vascular fibrous repair. Yet, the mechanisms are elusive. Here, we investigate alterations in the fibrous repair processes in type 2 diabetes atherosclerotic plaque extracellular matrix by combining multi-omics from the human Carotid Plaque Imaging Project cohort and functional studies. Plaques from type 2 diabetes patients have less collagen. Interestingly, lower levels of transforming growth factor-ß distinguish type 2 diabetes plaques and, in these patients, lower levels of fibrous repair markers are associated with cardiovascular events. Transforming growth factor-ß2 originates mostly from contractile vascular smooth muscle cells that interact with synthetic vascular smooth muscle cells in the cap, leading to collagen formation and vascular smooth muscle cell differentiation. This is regulated by free transforming growth factor-ß2 which is affected by hyperglycemia. Our findings underscore the importance of transforming growth factor-ß2-driven fibrous repair in type 2 diabetes as an area for future therapeutic strategies.
2型糖尿病与心血管疾病相关，可能是由于血管纤维修复受损。然而，其机制尚不清楚。在这里，我们通过结合人类颈动脉斑块成像项目队列的多组学和功能研究，调查2型糖尿病动脉粥样硬化斑块细胞外基质中纤维修复过程的改变。2型糖尿病患者的斑块中胶原蛋白较少。有趣的是，较低水平的转化生长因子-β可区分2型糖尿病斑块，并且在这些患者中，较低水平的纤维修复标志物与心血管事件相关。转化生长因子-β2主要来源于收缩性血管平滑肌细胞，这些细胞与帽状结构中的合成血管平滑肌细胞相互作用，导致胶原蛋白形成和血管平滑肌细胞分化。这由游离的转化生长因子-β2调节，而游离的转化生长因子-β2受高血糖影响。我们的研究结果强调了转化生长因子-β2驱动的纤维修复在2型糖尿病中的重要性，这是未来治疗策略的一个领域。
