B- and T-lymphocyte attenuator could be a new player in accelerated atherosclerosis associated with chronic kidney disease

Abstract

Background: In chronic kidney disease (CKD), cardiovascular morbi-mortality is higher than in general population. Atherosclerotic cardiovascular disease is accelerated in CKD, but specific CKD-related risk factors for atherosclerosis are unknown.  Methods: CKD patients from the NEFRONA study were used. We performed mRNA array from blood of patients free from atheroma plaque at baseline, with (n=10) and without (n=10) de novo atherosclerotic plaque development 2 years later. Selected mRNA candidates were validated in a bigger sample (n=148). Validated candidates were investigated in vivo in an experimental model of CKD-accelerated atherosclerosis, and in vitro in murine macrophages.</p>  Results: mRNA array analysis showed 92 up-regulated and 67 down-regulated mRNAs in samples from CKD patients with de novo plaque development. The functional analysis pointed to a paramount role of the immune response. The validation in a bigger sample confirmed that B- and T-lymphocyte co-inhibitory molecule (BTLA) down-regulation was associated with de novo plaque presence after 2 years. However, BTLA down-regulation was not found to be associated to atherosclerotic progression in patients with plaque already present at baseline. In a model of CKD-accelerated atherosclerosis, mRNA and protein expression levels of BTLA were significantly decreased in blood samples and atheroma plaques. Plaques from animals with CKD were bigger, had more infiltration of inflammatory cells, higher expression of IL6 and IL17 and less presence of collagen than plaques from control animals. Incubation of macrophages with rat uremic serum decreased BTLA expression.</p> Conclusions: BTLA could be a potential biomarker or therapeutic target for atherosclerosis incidence in CKD patients

The cytoplasmic sensor, the AIM2 inflammasome: A precise therapeutic target in vascular and metabolic diseases

“…Atherosclerotic plaque rupture and/or lesion erosion leads to acute vessel occlusion, myocardial infarction or ischaemic stroke, and their severe adverse clinical consequences (Falk, 2006). Extensive studies have established that unresolved inflammation underlies the development of atherosclerosis (Dolade et al, 2023; Edsfeldt et al, 2023; Han et al, 2023). Proinflammatory cytokines are synthesized by nearly all cells involved in the development of atherosclerosis, including endothelial cells (ECs) (Edsfeldt et al, 2023), macrophages (Dolade et al, 2023; Pekayvaz et al, 2023) and vascular smooth muscle cells (VSMCs) (Han et al, 2023).…”

“…Extensive studies have established that unresolved inflammation underlies the development of atherosclerosis (Dolade et al, 2023;Edsfeldt et al, 2023;Han et al, 2023). Proinflammatory cytokines are synthesized by nearly all cells involved in the development of atherosclerosis, including endothelial cells (ECs) (Edsfeldt et al, 2023), macrophages (Dolade et al, 2023;Pekayvaz et al, 2023) and vascular smooth muscle cells (VSMCs) (Han et al, 2023). In addition to atherosclerosis, inflammation worsens multiple other cardio-cerebrovascular diseases, including myocarditis (Chen, Zhu, et al, 2023), aneurysms (Kasprzak et al, 2023), Kawasaki disease (KD) (Brodeur et al, 2023) and arrhythmias (Bueto-Beni et al, 2023).…”