Ultrastructural Study of Platelet Behavior and Interrelationship in Sprouting and Intussusceptive Angiogenesis during Arterial Intimal Thickening Formation

Abstract

Platelets in atherosclerosis, bypass stenosis, and restenosis have been extensively assessed. However, a sequential ultrastructural study of platelets in angiogenesis during the early phases of these lesions has received less attention. Our objective was the study of platelets in angiogenesis and vessel regression during intimal thickening (IT) formation, a precursor process of these occlusive vascular diseases. For this purpose, we used an experimental model of rat occluded arteries and procedures for ultrastructural observation. The results show (a) the absence of platelet adhesion in the de-endothelialized occluded arterial segment isolated from the circulation, (b) that intraarterial myriad platelets contributed from neovessels originated by sprouting angiogenesis from the periarterial microvasculature, (c) the association of platelets with blood components (fibrin, neutrophils, macrophages, and eosinophils) and non-polarized endothelial cells (ECs) forming aggregates (spheroids) in the arterial lumen, (d) the establishment of peg-and-socket junctions between platelets and polarized Ecs during intussusceptive angiogenesis originated from the EC aggregates, with the initial formation of IT, and (e) the aggregation of platelets in regressing neovessels (‘transitory paracrine organoid’) and IT increases. In conclusion, in sprouting and intussusceptive angiogenesis and vessel regression during IT formation, we contribute sequential ultrastructural findings on platelet behavior and relationships, which can be the basis for further studies using other procedures.

Comparison of the Behavior of Perivascular Cells (Pericytes and CD34+ Stromal Cell/Telocytes) in Sprouting and Intussusceptive Angiogenesis

“…In these junctions, pericytes form the peg and ECs form the socket in their abluminal surface [ 3 , 74 , 204 , 205 ]. A similar increase in this type of union has been described between vascular smooth muscle cells and ECs in some processes, such as arterial intimal thickening [ 206 ].…”

SGLT2 inhibitor improves the prognosis of patients with coronary heart disease and prevents in-stent restenosis

“…As a result of stent implantation, the physiological barrier function of EC is impaired due to changes in cell connectivity, and its ability to regulate vascular tone, control inflammation, maintain lipid and tissue fluid homeostasis, and prevent thrombosis is reduced ( 91 , 92 ). At the same time, SMC changed from contractive phenotype to synthetic phenotype ( 93 ).…”