Injury to the tunica media initiates atherogenesis in the presence of hyperlipidemia

Abstract

Background and aimsFatty streaks initiating the formation of atheromatous plaque appear in the tunica intima. The tunica media is not known to be a nidus for lipid accumulation initiating atherogenesis. We assessed changes to the tunica media in response to a micro-injury produced in the pig aorta. In addition, we assessed human carotid endarterectomy plaques for indication of atheroma initiation in the tunica media.MethodsThree healthy landrace female pigs underwent laparotomy to inject autologous blood and create micro-hematomas at 6 sites within the tunica media of the infrarenal abdominal aorta. These pigs were fed a high-fat diet (HFD) for 4–12 weeks. Post-mortem aortas from all pigs, including a control group of healthy pigs, were serially stained to detect lipid deposits, vasa vasora (VV), immune cell infiltration and inflammatory markers, as well as changes to the vascular smooth muscle cell (vSMC) compartment. Moreover, 25 human carotid endarterectomy (CEA) specimens were evaluated for their lipid composition in the tunica media and intima.ResultsHigh lipid clusters, VV density, and immune cell infiltrates were consistently observed at 5 out of 6 injection sites under prolonged hyperlipidemia. The hyperlipidemic diet also affected the vSMC compartment in the tunica media adjacent to the tunica adventitia, which correlated with VV invasion and immune cell infiltration. Analysis of human carotid specimens post-CEA indicated that 32% of patients had significantly greater atheroma in the tunica media than in the arterial intima.ConclusionThe arterial intima is not the only site for atherosclerosis initiation. We show that injury to the media can trigger atherogenesis.

Assessment of the aortic tunica media histological changes in relation with the cause of death

“…Medium tunic is the most prominent and the most important of the three distinct constituent layers of the aortic wall structure. It is placed in the middle of the wall, being separated from the two other layers by internal and external elastic laminae [ 1 , 2 , 3 , 4 ]. Of the complex vascular mechanic functions of the aortic wall, the tunica media is crucial for the determination of the tensile strength, the stiffness and its non-linear elasticity [ 5 , 6 , 7 , 8 , 9 ].…”

“…The most important and primary load-bearing component structures are elastic fibers (FE), collagen fibers (FCOL), and smooth muscle fibers (FM) [1,[10][11][12]. FE and FCOL are the primary key elements of the extracellular matrix (ECM) of the aorta, making up around 50% of the dry weight of normal arterial tissue [13][14][15][16].…”