Chronic cardiometabolic assaults during type 2 diabetes (T2D) and obesity induce a progenitor cell imbalance in the circulation characterized by overproduction and release of pro-inflammatory monocytes and granulocytes from the bone marrow alongside aberrant differentiation and mobilization of pro-vascular progenitor cells that generate downstream progeny for the coordination of blood vessel repair. This imbalance can be detected in the peripheral blood of individuals with established T2D and severe obesity using multiparametric flow cytometry analyses to discern pro-inflammatory vs. pro-angiogenic progenitor cell subsets identified by high aldehyde dehydrogenase activity, a conserved progenitor cell protective function, combined with lineage-restricted cell surface marker analyses. Recent evidence suggests that progenitor cell imbalance can be reversed by treatment with pharmacological agents or surgical interventions that reduce hyperglycaemia or excess adiposity. In this state-of-the-art review, we present current strategies to assess the progression of pro-vascular regenerative cell depletion in peripheral blood samples of individuals with T2D and obesity and we summarize novel clinical data that intervention using sodium-glucose co-transporter 2 inhibition or gastric bypass surgery can efficiently restore cell-mediated vascular repair mechanisms associated with profound cardiovascular benefits in recent outcome trials. Collectively, this thesis generates a compelling argument for early intervention using current pharmacological agents to prevent or restore imbalanced circulating progenitor content and maintain vascular regenerative cell trafficking to sites of ischaemic damage. This conceptual advancement may lead to the design of novel therapeutic approaches to prevent or reverse the devastating cardiovascular comorbidities currently associated with T2D and obesity.

中文翻译：

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心脏代谢疾病中的血管修复和再生

2 型糖尿病 (T2D) 和肥胖期间的慢性心脏代谢攻击导致循环中的祖细胞失衡，其特征是骨髓中促炎性单核细胞和粒细胞的过度产生和释放，以及在下游产生的促血管祖细胞的异常分化和动员后代用于协调血管修复。可以使用多参数流式细胞术分析在患有 T2D 和严重肥胖的个体的外周血中检测到这种不平衡，以辨别由高醛脱氢酶活性（一种保守的祖细胞保护功能）鉴定的促炎与促血管生成祖细胞亚群，结合具有谱系限制的细胞表面标记分析。最近的证据表明，祖细胞失衡可以通过药物治疗或减少高血糖或过度肥胖的手术干预来逆转。在这篇最先进的综述中，我们提出了评估 T2D 和肥胖个体外周血样本中促血管再生细胞耗竭进展的当前策略，并总结了使用钠-葡萄糖共同干预的新临床数据。在最近的结果试验中，转运蛋白 2 抑制或胃旁路手术可以有效地恢复与显着心血管益处相关的细胞介导的血管修复机制。集体，本论文为使用当前药物进行早期干预以预防或恢复不平衡的循环祖细胞含量并维持血管再生细胞向缺血性损伤部位的运输提供了令人信服的论据。这种概念上的进步可能会导致设计新的治疗方法来预防或逆转目前与 T2D 和肥胖相关的破坏性心血管合并症。