Molecular Mechanisms Underlying Pathological and Therapeutic Roles of Pericytes in Atherosclerosis

Abstract

Pericytes are multipotent mesenchymal stromal cells playing an active role in angiogenesis, vessel stabilisation, maturation, remodelling, blood flow regulation and are able to trans-differentiate into other cells of the mesenchymal lineage. In this review, we summarised recent data demonstrating that pericytes play a key role in the pathogenesis and development of atherosclerosis (AS). Pericytes are involved in lipid accumulation, inflammation, growth, and vascularization of the atherosclerotic plaque. Decreased pericyte coverage, endothelial and pericyte dysfunction is associated with intraplaque angiogenesis and haemorrhage, calcification and cholesterol clefts deposition. At the same time, pericytes can be used as a novel therapeutic target to promote vessel maturity and stability, thus reducing plaque vulnerability. Finally, we discuss recent studies exploring effective AS treatments with pericyte-mediated anti-atherosclerotic, anti-inflammatory and anti-apoptotic effects.

Encompassing view of spatial and single-cell RNA-seq renews the role of the microvasculature in human atherosclerosis

“…1g ). The comprehensive transcriptome alterations of periycytes was somewhat surprising as their role in Atherosclerosis is understudied 15 . However, the relatively diminished gene expression profile observed in pericytes compared to other cellular counterparts, coupled with their transcriptional resemblance to vascular smooth muscle cells (VSMCs), potentially masked the distinctive impact of pericytes.…”

Deciphering the connection: Diabetes, pericyte dysfunction, and their impact on cardiovascular health

“…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 …”

“…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 …”

“…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.…”

“…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 diabetesrelated 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).…”