The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation

Abstract

Background and aims: Endothelial surface glycocalyx shedding plays a role in endothelial dysfunction and increases vessel wall permeability, which can lead to inflammation and atherogenesis. We sought to elucidate whether a high fat diet (HFD) or disturbed blood flow conditions, both of which are atherogenic risk factors, would contribute more detrimentally to pre-atherosclerotic loss of endothelial glycocalyx integrity and vascular inflammation. Methods: Six to seven week-old C57BL/6-background apolipoprotein-E-knockout (ApoE-KO) male mice were either fed a chow diet, fed a modified Western HFD, and/or subjected to a partial left carotid artery (LCA) ligation procedure to induce disturbed blood flow patterns in the LCA. Mice were sacrificed after 1 week of experimental conditions. Both LCA and right carotid artery (RCA) vessels were dissected and preserved to compare glycocalyx coverage and thickness as well as macrophage accumulation in carotid arterial walls amongst and between cohorts. Results: Glycocalyx coverage of the endothelium was significantly reduced in the LCAs of HFD fed mice when compared to the control. More significant reduction in glycocalyx coverage occurred in the LCAs of mice exposed to disturbed flow by partial LCA ligation when compared to the control. No differences were found in glycocalyx coverage of RCAs from all cohorts. Regarding inflammation, no difference in macrophage accumulation in carotid arterial walls was observed when comparing the LCAs and RCAs of control and HFD fed mice. However, macrophage infiltration in vessel walls showed a 20-fold increase in the LCAs exposed to disturbed flow following ligation, when compared to control LCAs, while no such statistical difference was observed between the RCAs of the group. Conclusions: In our mouse model, endothelial glycocalyx integrity was compromised more by disturbed blood flow patterns than by exposure of the carotid vessel to HFD conditions. The pathophysiological implications include endothelial dysfunction, which correlates to macrophage infiltration in vessel walls and promotes atherogenesis.

Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction

“…Additionally, mechanotransducers, such as the endothelial glycocalyx (GCX), have been shown to be degraded in response to ischemiareperfusion (Rubio-Gayosso et al, 2006), which may exacerbate issues of proper mechanotransduction. Impaired mechanotransduction may even contribute to the occurrence of ischemic stroke, as the development of blood vessel plaques, which can rupture and lead to ischemic stroke, are known to occur in areas of disturbed blood flow characterized by altered mechanotransduction and degraded GCX layers (van den Berg et al, 2009;Cancel et al, 2016;Harding et al, 2018;Mitra et al, 2018). It is therefore vital to understand the impact of endothelial mechanotransduction in both stroke pathology and occurrence, which will be addressed later in the review.…”

High Fat Diet Dysbiotic Mechanism of Decreased Gingival Blood Flow

“…Elevated proinflammatory cytokines production induces increased activity and expression of MMP. Previously conducted experimental studies have found that HFD causes loss of vascular elasticity, primarily due to deposition of harmful substances in the walls of blood vessels, which in turn leads to reduction of blood flow ( Declèves et al, 2013 ; Mitra et al, 2018 ; Yuan et al, 2019 ). Since MMPs are one of the factors causing the occlusion as well as damage of blood vessels and periodontal tissue, MMP-2, MMP-9, and TIMP-2 expression was measured in periodontal mice tissue.…”

“…Disturbance in local vascular flow is in correlation with inhibition of tissue oxygenation and reduction of microvascular blood flow. Disorder of blood flow activity is noted to be an early marker for progression of microvascular pathology ( Clough et al, 2017 ; Mitra et al, 2018 ; Ohsugi et al, 2019 ). HFD contributes to endothelial dysfunction and loss of integrity ( Clough et al, 2017 ; Mitra et al, 2018 ; Münch et al, 2019 ) it has been shown that 2h after a fatty meal, HFD causes endothelial damage by vascular occlusion and leads to decreased blood flow ( Bui et al, 2010 ; Münch et al, 2019 ).…”

Inflammation and enhanced atherogenesis in the carotid artery with altered blood flow in an atherosclerosis‐resistant mouse strain

“…Compared to the carotid arteries of Apoe −/− mice that received no surgical manipulation, the ligated vessels of both strains showed more lipid deposition in the arterial wall (Figures 1 and 4). A recent study has shown that endothelial glycocalyx integrity of partially ligated carotid artery of B6-Apoe −/− mice is compromised more by disturbed blood flow than by exposure to a Western diet (Mitra et al, 2018). Increased endothelial permeability would result in more ApoB-containing lipoprotein accumulation in the walls of ligated arteries (Brown et al, 2004).…”