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Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model.

ABSTRACT: Previous experiments suggest that both increased endothelial cell apoptosis and endothelial surface glycocalyx shedding could play a role in the endothelial dysfunction and inflammation of athero-prone regions of the vasculature. We sought to elucidate the possibly synergistic mechanisms by which endothelial cell apoptosis and glycocalyx shedding promote atherogenesis.4- to 6-week old male C57Bl/6 apolipoprotein E knockout (ApoE(-/-)) mice were fed a Western diet for 10 weeks and developed plaques in their brachiocephalic arteries.Glycocalyx coverage and thickness were significantly reduced over the plaque region compared to the non-plaque region (coverage plaque: 71 ± 23%, non-plaque: 97 ± 3%, p = 0.02; thickness plaque: 0.85 ± 0.15 ?m, non-plaque: 1.2 ± 0.21 ?m, p = 0.006). Values in the non-plaque region were not different from those found in wild type mice fed a normal diet (coverage WT: 92 ± 3%, p = 0.7 vs. non-plaque ApoE(-/-), thickness WT: 1.1 ± 0.06 ?m, p = 0.2 vs. non-plaque ApoE(-/-)). Endothelial cell apoptosis was significantly increased in ApoE(-/-) mice compared to wild type mice (ApoE(-/-):64.3 ± 33.0, WT: 1.1 ± 0.5 TUNEL-pos/cm, p = 2 × 10(-7)). The number of apoptotic endothelial cells per unit length was 2 times higher in the plaque region than in the non-plaque region of the same vessel (p = 3 × 10(-5)). Increased expression of matrix metalloproteinase 9 co-localized with glycocalyx shedding and plaque buildup.Our results suggest that, in concert with endothelial apoptosis that increases lipid permeability, glycocalyx shedding initiated by inflammation facilitates monocyte adhesion and macrophage infiltration that promote lipid retention and the development of atherosclerotic plaques.

SUBMITTER: Cancel LM

PROVIDER: S-EPMC5035621 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model.

Cancel Limary M LM Ebong Eno E EE Mensah Solomon S Hirschberg Carly C Tarbell John M JM

Atherosclerosis 20160801

<h4>Background and aims</h4>Previous experiments suggest that both increased endothelial cell apoptosis and endothelial surface glycocalyx shedding could play a role in the endothelial dysfunction and inflammation of athero-prone regions of the vasculature. We sought to elucidate the possibly synergistic mechanisms by which endothelial cell apoptosis and glycocalyx shedding promote atherogenesis.<h4>Methods</h4>4- to 6-week old male C57Bl/6 apolipoprotein E knockout (ApoE(-/-)) mice were fed a W ...[more]

PMID: 27529818

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Project description:In diabetes mellitus (DM) patients, the morbidity of infectious disease is increased, and these infections can easily progress from local to systemic infection. Sepsis is a characteristic of organ failure related to microcirculation disorders resulting from endothelial cell injury, whose most frequent comorbidity in patients is DM. The aim of the present study was to evaluate the influence of infection on DM-induced microvascular damage on inflammation and pulmonary endothelial structure using an experimental endotoxemia model. Lipopolysaccharide (LPS; 15 mg/kg) was injected intraperitoneally into 10-week-old male C57BLKS/J Iar- + lepr db /lepr db (db/db) mice and into C57BLKS/J Iar-m + / + lepr db (db/ +) mice, which served as the littermate non-diabetic control. At 48 h after LPS administration, the survival rate of db/db mice (0%, 0/10) was markedly lower (P < 0.05) than that of the db/ + mice (75%, 18/24), whereas the survival rate was 100% in both groups 24 h after LPS administration. In control mice, CD11b-positive cells increased at 6 h after LPS administration; by comparison, the number of CD11b-positive cells increased gradually in db/db mice until 12 h after LPS injection. In the control group, the number of Iba-1-positive cells did not significantly increase before and at 6, 12, and 24 h after LPS injection. Conversely, Iba-1-positive cells continued to increase until 24 h after LPS administration, and this increase was significantly greater than that in the control mice. Expression of Ext1, Csgalnact1, and Vcan related to endothelial glycocalyx synthesis was significantly lower in db/db mice than in the control mice before LPS administration, indicating that endothelial glycocalyx synthesis is attenuated in db/db/mice. In addition, ultrastructural analysis revealed that endothelial glycocalyx was thinner in db/db mice before LPS injection. In conclusion, in db/db mice, the endothelial glycocalyx is already injured before LPS administration, and migration of inflammatory cells is both delayed and expanded. This extended inflammation may be involved in endothelial glycocalyx damage due to the attenuation of endothelial glycocalyx synthesis.

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Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model.

Publications

Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model.

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