Nuria Dolade, Sandra Rayego-Mateos, Alicia Garcia-Carrasco, Maryse Guerin, Jose-Luis Martín-Ventura, Marta Ruiz-Ortega, Pierre-Louis Tharaux, Jose Manuel Valdivielso
{"title":"B和T淋巴细胞衰减器可能是与慢性肾脏疾病相关的加速动脉粥样硬化的一个新参与者。","authors":"Nuria Dolade, Sandra Rayego-Mateos, Alicia Garcia-Carrasco, Maryse Guerin, Jose-Luis Martín-Ventura, Marta Ruiz-Ortega, Pierre-Louis Tharaux, Jose Manuel Valdivielso","doi":"10.1042/CS20230399","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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><p><strong>Results: </strong>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 with 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><p><strong>Conclusions: </strong>BTLA could be a potential biomarker or therapeutic target for atherosclerosis incidence in CKD patients.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":null,"pages":null},"PeriodicalIF":6.7000,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"B- and T-lymphocyte attenuator could be a new player in accelerated atherosclerosis associated with chronic kidney disease.\",\"authors\":\"Nuria Dolade, Sandra Rayego-Mateos, Alicia Garcia-Carrasco, Maryse Guerin, Jose-Luis Martín-Ventura, Marta Ruiz-Ortega, Pierre-Louis Tharaux, Jose Manuel Valdivielso\",\"doi\":\"10.1042/CS20230399\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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><p><strong>Results: </strong>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 with 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><p><strong>Conclusions: </strong>BTLA could be a potential biomarker or therapeutic target for atherosclerosis incidence in CKD patients.</p>\",\"PeriodicalId\":10475,\"journal\":{\"name\":\"Clinical science\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2023-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1042/CS20230399\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1042/CS20230399","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
B- and T-lymphocyte attenuator could be a new player in accelerated atherosclerosis associated with chronic kidney disease.
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.
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 with 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.
Conclusions: BTLA could be a potential biomarker or therapeutic target for atherosclerosis incidence in CKD patients.
期刊介绍:
Translating molecular bioscience and experimental research into medical insights, Clinical Science offers multi-disciplinary coverage and clinical perspectives to advance human health.
Its international Editorial Board is charged with selecting peer-reviewed original papers of the highest scientific merit covering the broad spectrum of biomedical specialities including, although not exclusively:
Cardiovascular system
Cerebrovascular system
Gastrointestinal tract and liver
Genomic medicine
Infection and immunity
Inflammation
Oncology
Metabolism
Endocrinology and nutrition
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