In the intricate tapestry of human biology, diabetes mellitus silently threads its way, casting unseen webs across the expanse of global health.¹ This enduring metabolic disorder, characterized by elevated blood glucose levels, poses a challenge that extends beyond its well-documented impact on blood vessels. Unbeknownst to many, diabetes conducts a symphony of disruption, particularly affecting the custodians of vascular harmony – the pericytes.

Known alternately as Rouget cells or perivascular cells, these pericytes are not mere passive spectators in the Grand Theater of the human body. Enveloping the microvascular basement membrane throughout the body, they were first perceived as structural support for blood vessels.² However, as the pages of scientific exploration turn, their dynamic nature emerges, revealing involvement in crucial processes such as angiogenesis, vascular stability, and immune response modulation.³

The cardiovascular system, a delicate ballet of physiologic processes, relies on the intricate equilibrium between endothelial cells and pericytes for its integrity. Pericytes, in their pivotal role, regulate blood flow, vessel permeability, and tissue perfusion, maintaining vascular function.^{4, 5}

This delicate balance, however, is disrupted by hyperglycemia, the hallmark of diabetes, which casts a malevolent shadow, triggering events that wreak havoc on pericyte function. Oxidative stress emerges as a primary antagonist, inducing the overproduction of reactive oxygen species that compromises pericyte support in maintaining vascular stability. Inflammation, driven by the relentless onslaught of hyperglycemia, causes phenotypic changes in pericytes, compromising their ability to regulate vascular tone and permeability.⁶ Advanced glycation end-products (AGEs) further disrupt the once harmonious communication between pericytes and endothelial cells, throwing the entire cardiovascular system into disarray.^{7, 8}

The symphony of pericyte–endothelial crosstalk, once melodious, now falters in the face of diabetes. Dysregulated angiogenesis leads to abnormal vessel formation and impaired tissue perfusion, casting a dark shadow over the previously vibrant landscape of vascular homeostasis. Capillary rarefaction ensues, reducing capillary density and exacerbating organ damage, especially in highly vascularized organs like the heart.⁹

Yet, amidst the chaos, potential opportunities for new treatment approaches emerge. Pericytes, it seems, play a crucial role in the saga of myocardial ischemia. Studies suggest their involvement in inflammation modulation, angiogenesis, and the regeneration of the infarcted heart.¹⁰ The flicker of potential therapeutic avenues suggests that pericytes might hold the key to unraveling the mysteries of cardiovascular regenerative medicine.¹¹

In addition, these specialized cells are also found in the microvasculature of both retinal and renal systems, again playing roles in the vascular complications of diabetes.¹² In the retina, pericytes are essential for the formation and maintenance of the blood–retinal barrier (BRB).¹³ The BRB regulates the passage of nutrients and ions between the blood and the neural tissue of the retina, ensuring a stable microenvironment crucial for optimal visual function. Pericytes contribute to the structural support of capillaries, regulate blood flow, and participate in the maintenance of vascular permeability, thus preventing leakage that could lead to vision-threatening conditions such as diabetic retinopathy.¹⁴

Correspondingly, in the kidneys, pericytes are key players in the regulation of renal blood flow and glomerular filtration.¹⁵ They are integral components of the renal vasculature, contributing to the structural integrity of capillaries in the glomerulus. Pericytes modulate blood pressure in the kidneys, affecting the filtration of waste products and maintenance of electrolyte balance. Dysfunction of pericytes in the renal system is associated with various renal disorders, including diabetic nephropathy.

In summation, pericytes are indispensable in preserving the normal functioning of the retina and kidneys, highlighting their pivotal role in maintaining vascular homeostasis and preventing the onset of debilitating ocular and renal conditions.

As the scientific tale unfolds, it becomes evident that understanding the impact of diabetes on pericyte function opens doors to potential therapeutic interventions. Antioxidant therapies, anti-inflammatory compounds, and strategies targeting AGE formation become the knights in shining armor, venturing to preserve pericyte function and reduce the looming threat of diabetes-related cardiovascular complications.²

The development of novel therapeutic modalities offers the potential to enhance angiogenesis and microvascular perfusion. The intricate connection between diabetes and cardiovascular disease, illuminated by the critical role of pericytes, hints at a future where innovative approaches could revolutionize the management of cardiovascular complications in people battling the relentless adversary that is diabetes (Figure 1).

在错综复杂的人类生物学中，糖尿病悄然蔓延，在全球健康领域撒下看不见的网。¹这种持久的代谢紊乱以血糖水平升高为特征，所带来的挑战超出了其对血管影响的详细记录。许多人不知道的是，糖尿病会带来破坏，特别是影响血管和谐的守护者——周细胞。

这些周细胞也被称为 Rouget 细胞或血管周围细胞，它们不仅仅是人体大剧院中的被动观众。它们包裹着全身的微血管基底膜，最初被认为是血管的结构支撑。²然而，随着科学探索的一页一页翻开，它们的动态性质逐渐显现，揭示了它们参与血管生成、血管稳定性和免疫反应调节等关键过程。³

心血管系统是一场微妙的生理过程的芭蕾舞，其完整性依赖于内皮细胞和周细胞之间复杂的平衡。周细胞发挥着关键作用，调节血流、血管通透性和组织灌注，维持血管功能。^{4, 5}

然而，这种微妙的平衡被高血糖破坏了，高血糖是糖尿病的标志，它投下了恶毒的阴影，引发了对周细胞功能造成严重破坏的事件。氧化应激作为主要拮抗剂出现，诱导活性氧的过量产生，从而损害周细胞对维持血管稳定性的支持。由高血糖的持续攻击驱动的炎症会引起周细胞的表型变化，损害其调节血管张力和通透性的能力。⁶晚期糖基化终产物 (AGE) 进一步破坏周细胞和内皮细胞之间一度和谐的通讯，使整个心血管系统陷入混乱。^{7, 8}

周细胞与内皮细胞串扰的交响乐曾经是悠扬的，现在在糖尿病面前变得动摇了。血管生成失调导致血管形成异常和组织灌注受损，给以前充满活力的血管稳态蒙上了阴影。随后毛细血管稀疏，降低毛细血管密度并加剧器官损伤，特别是在心脏等高度血管化的器官中。⁹

然而，在混乱之中，新治疗方法的潜在机会出现了。周细胞似乎在心肌缺血的传奇中发挥着至关重要的作用。研究表明它们参与炎症调节、血管生成和梗塞心脏的再生。¹⁰潜在治疗途径的闪烁表明，周细胞可能是解开心血管再生医学之谜的关键。¹¹

此外，这些特化细胞也存在于视网膜和肾脏系统的微血管系统中，再次在糖尿病的血管并发症中发挥作用。¹²在视网膜中，周细胞对于血视网膜屏障 (BRB) 的形成和维持至关重要。¹³ BRB 调节血液和视网膜神经组织之间营养物质和离子的通道，确保稳定的微环境，这对于最佳视觉功能至关重要。周细胞有助于毛细血管的结构支撑、调节血流并参与血管通透性的维持，从而防止可能导致糖尿病视网膜病变等危及视力的疾病的渗漏。¹⁴

相应地，在肾脏中，周细胞是调节肾血流量和肾小球滤过的关键角色。¹⁵它们是肾脉管系统不可或缺的组成部分，有助于肾小球毛细血管的结构完整性。周细胞调节肾脏的血压，影响废物的过滤和电解质平衡的维持。肾脏系统周细胞功能障碍与各种肾脏疾病有关，包括糖尿病肾病。

总之，周细胞对于维持视网膜和肾脏的正常功能是不可或缺的，突出了它们在维持血管稳态和预防眼部和肾脏衰弱疾病的发生方面的关键作用。

随着科学故事的展开，很明显，了解糖尿病对周细胞功能的影响为潜在的治疗干预措施打开了大门。抗氧化疗法、抗炎化合物和针对 AGE 形成的策略成为披着闪亮盔甲的骑士，冒险保护周细胞功能并减少糖尿病相关心血管并发症的迫在眉睫的威胁。²

新型治疗方式的发展提供了增强血管生成和微血管灌注的潜力。周细胞的关键作用阐明了糖尿病和心血管疾病之间的错综复杂的联系，这暗示着未来创新方法可能会彻底改变人们与糖尿病这一无情对手的心血管并发症的管理（图1）。