Unit of Vascular Biology and Regenerative Medicine, IRCCS Centro Cardiologico Monzino, I-20138- Milan, Italy.
Unit of Diabetes, Endocrine and Metabolic Diseases, IRCCS Centro Cardiologico Monzino, I-20138- Milan, Italy.
Int J Mol Sci. 2020 May 29;21(11):3864. doi: 10.3390/ijms21113864.
Diabetes strongly contributes to the development of cardiovascular disease, the leading cause of mortality and morbidity in these patients. It is widely accepted that hyperglycemia impairs hematopoietic stem/progenitor cell (HSPC) mobilization from the bone marrow (BM) by inducing stem cell niche dysfunction. Moreover, a recent study demonstrated that type 2 diabetic patients are characterized by significant depletion of circulating provascular progenitor cells and increased frequency of inflammatory cells. This unbalance, potentially responsible for the reduction of intrinsic vascular homeostatic capacity and for the establishment of a low-grade inflammatory status, suggests that bone BM-derived HSPCs are not only victims but also active perpetrators in diabetic complications. In this review, we will discuss the most recent literature on the molecular mechanisms underpinning hyperglycemia-mediated BM dysfunction and differentiation abnormality of HSPCs. Moreover, a section will be dedicated to the new glucose-lowering therapies that by specifically targeting the culprits may prevent or treat diabetic complications.
糖尿病是导致心血管疾病的主要原因，也是这些患者死亡和发病的主要原因。人们普遍认为，高血糖通过诱导干细胞龛功能障碍，从而损害造血干/祖细胞（HSPC）从骨髓（BM）中的动员。此外，最近的一项研究表明，2 型糖尿病患者的特征是循环前血管祖细胞明显耗竭，炎症细胞频率增加。这种失衡可能导致内在血管稳态能力降低，并导致低度炎症状态的建立，表明 BM 来源的 HSPC 不仅是受害者，而且是糖尿病并发症的积极肇事者。在这篇综述中，我们将讨论关于高血糖介导的 BM 功能障碍和 HSPC 分化异常的最新文献。此外，还有一部分将专门讨论新的降糖治疗方法，这些方法通过专门针对罪魁祸首，可能预防或治疗糖尿病并发症。
