New mechanisms of chronic kidney disease-associated vascular calcification / 生理学报

Vascular calcification is the crucial factor of high cardiovascular disease morbidity and mortality in patients with chronic kidney disease (CKD), which causes a huge medical and economic burden. It is urgent to explore its pathogenesis and intervention methods. CKD-associated vascular calcification is an ectopic osteogenesis process actively regulated by multiple cells. Vascular smooth muscle cells (VSMCs) undergo osteogenic differentiation in a pro-calcification environment, and secrete matrix vesicles to form calcium and phosphorus crystal deposition sites, which are key events in the development of CKD-associated vascular calcification. This article reviews the new mechanism and technology of CKD-associated vascular calcification and discusses the role of the myokine Irisin in CKD-associated vascular calcification.

Consensus and controversy on research progress and clinical practice of vascular calcification / 生理学报

Vascular calcification is an active and complex pathological process regulated by several factors. Vascular calcification is closely related to the incidence and mortality of the cardiovascular disease, chronic kidney disease and other diseases, which affects multiple organs and systems, thus affecting people's health. Therefore, more and more attention is paid to vascular calcification. At present, the pathogenesis and clinical practice of vascular calcification have been continuously improved, which mainly includes calcium and phosphorus imbalance theory, vascular smooth muscle cell transdifferentiation theory, bone homeostasis imbalance theory, epigenetic regulation theory, inflammation theory, extracellular matrix theory, new cell fate theory and so on. However, there are still many unsolved problems. Since the occurrence and development of vascular calcification affect multiple organs and systems, this expert consensus gathered clinicians and basic research experts engaged in the study of vascular calcification in order to summarize the progress of various disciplines related to vascular calcification in recent years. The purpose of this consensus is to systematically summarize the latest research progress, treatment consensus and controversy of vascular calcification from the aspects of epidemiology, pathogenesis, prevention and treatment, so as to provide theoretical basis and clinical enlightenment for in-depth research in this field.

Bax inhibitor 1 inhibits vascular calcification in mice by activating optic atrophy 1 expression / 南方医科大学学报

OBJECTIVE@#To investigate the effects of Bax inhibitor 1 (BI- 1) and optic atrophy protein 1 (OPA1) on vascular calcification (VC).@*METHODS@#Mouse models of VC were established in ApoE-deficient (ApoE-/-) diabetic mice by high-fat diet feeding for 12 weeks followed by intraperitoneal injections with Nε-carboxymethyl-lysine for 16 weeks. ApoE-/- mice (control group), ApoE-/- diabetic mice (VC group), ApoE-/- diabetic mice with BI-1 overexpression (VC + BI-1TG group), and ApoE-/- diabetic mice with BI-1 overexpression and OPA1 knockout (VC+BI-1TG+OPA1-/- group) were obtained for examination of the degree of aortic calcification using von Kossa staining. The changes in calcium content in the aorta were analyzed using ELISA. The expressions of Runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein 2 (BMP-2) were detected using immunohistochemistry, and the expression of cleaved caspase-3 was determined using Western blotting. Cultured mouse aortic smooth muscle cells were treated with 10 mmol/L β-glycerophosphate for 14 days to induce calcification, and the changes in BI-1 and OPA1 protein expressions were examined using Western blotting and cell apoptosis was detected using TUNEL staining.@*RESULTS@#ApoE-/- mice with VC showed significantly decreased expressions of BI-1 and OPA1 proteins in the aorta (P=0.0044) with obviously increased calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 (P= 0.0041). Overexpression of BI-1 significantly promoted OPA1 protein expression and reduced calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 (P=0.0006). OPA1 knockdown significantly increased calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 in the aorta (P=0.0007).@*CONCLUSION@#BI-1 inhibits VC possibly by promoting the expression of OPA1, reducing calcium deposition and inhibiting osteogenic differentiation and apoptosis of the vascular smooth muscle cells.

Effect of spironolactone on the progression of coronary calcification in peritoneal dialysis patients: a pilot study / Efeito da espironolactona na progressão da calcificação coronariana em pacientes em diálise peritoneal: um estudo piloto

ABSTRACT Introduction: There is evidence that aldosterone plays a role in the pathogenesis of vascular calcification. The aim of this study was to evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, on the progression of coronary calcification (CC) in peritoneal dialysis patients and to identify the factors involved in this progression. Methods: Thirty-three patients with a coronary calcium score (CCS) ≥ 30, detected through multi-detector computed tomography (MDCT) and expressed in Agatston units, were randomly assigned to a group receiving 25mg spironolactone per day for 12 months (spironolactone group) and a control group not receiving this drug. The primary outcome was a percentage change in CCS from baseline to end of the study (relative progression), when a further MDCT was conducted. Patients who had progression of CC were compared with those who did not progress. Results: Sixteen patients, seven in the spironolactone group and nine in the control group, concluded the study. The relative progression of the CCS was similar in both groups, 17.2% and 27.5% in the spironolactone and control groups respectively. Fifty-seven percent of the treated patients and 67% of those in the control group presented progression in the CC scores (p = 0.697). Progressor patients differed from non-progressors because they presented higher levels of calcium and low-density lipoprotein cholesterol and lower levels of albumin. Conclusion: In peritoneal dialysis patients, spironolactone did not attenuate the progression of CC. However, large-scale studies are needed to confirm this observation. Disorders of mineral metabolism and dyslipidemia are involved in the progression of CC.

RESUMO Introdução: Existem evidências de que a aldosterona exerça um papel na patogênese da calcificação vascular. O objetivo deste estudo foi avaliar o efeito da espironolactona, um antagonista do receptor mineralocorticoide, na progressão da calcificação coronariana (CC) de pacientes em diálise peritoneal, e identificar os fatores envolvidos nessa progressão. Métodos: Trinta e três pacientes com escore de cálcio coronariano (ECC) ≥ 30, detectado por tomografia computadorizada com múltiplos detectores (TCMD) e expresso em unidades de Agatston, foram randomizados para um grupo que recebeu 25 mg de espironolactona por dia durante 12 meses (grupo espironolactona) e um grupo controle que não recebeu este medicamento. O desfecho primário foi a mudança percentual do ECC do início para o final do estudo (progressão relativa), quando uma nova TCMD foi realizada. Os pacientes que tiveram progressão de CC foram comparados com aqueles que não progrediram. Resultados: Dezesseis pacientes, sete no grupo espironolactona e nove no grupo controle, concluíram o estudo. A progressão relativa do ECC foi semelhante nos dois grupos, 17,2% e 27,5% nos grupos espironolactona e controle, respectivamente. Cinquenta e sete por cento dos pacientes tratados e 67% daqueles no grupo controle apresentaram progressão nos escores de CC (p = 0,697). Os pacientes progressores diferiram dos não progressores porque apresentaram níveis séricos mais elevados de cálcio e LDL-colesterol e menores níveis de albumina. Conclusão: Em pacientes em diálise peritoneal, a espironolactona não atenuou a progressão da CC. No entanto, estudos em grande escala são necessários para confirmar essa observação. Distúrbios do metabolismo mineral e dislipidemia estão envolvidos na progressão da CC.

Frequência e fatores relacionados ao índice tornozelo-braquial aberrante em diabéticos / Frequency and factors associated with high Ankle-Brachial Index in diabetic patients

Resumo Contexto O índice tornozelo-braquial (ITB) é um exame de rastreamento da doença arterial obstrutiva periférica, sendo também utilizado para avaliar o risco cardiovascular. Em diabéticos, a interpretação do exame é difícil pela possibilidade de índice aberrante devido à calcificação da camada média arterial. Objetivo Encontrar a frequência de ITB aberrante em diabéticos e verificar sua associação com variáveis sociodemográficas. Métodos Estudo descritivo com entrevista e aferição de ITB de 309 pacientes diabéticos tipo 2, acompanhados no centro de referência Centro de Diabetes e Endocrinologia da Bahia (CEDEBA), Salvador, BA, Brasil. Foi estudada a frequência e a relação entre o ITB aberrante e variáveis sociodemográficas, como sexo, idade e renda familiar. Utilizou-se um ponto de corte para ITB aberrante de 1,3. As variáveis contínuas foram dicotomizadas. Para a análise estatística, utilizou-se o teste do qui-quadrado, considerando significante um p ≤ 0,05. Resultados Entre os 309 pacientes entrevistados, 65% eram mulheres, 26% haviam cursado ensino médio completo e 77% tinham renda familiar igual ou menor que três salários mínimos. A frequência de ITB aberrante ≥ 1,3 foi 16,5%. Não foram encontradas correlações estatisticamente significantes nas análises bivariadas entre o ITB aberrante (≥ 1,3) e as variáveis sociodemográficas estudadas (sexo, idade, tempo de duração de diabetes melito, renda familiar e escolaridade). Conclusões A frequência de ITB aberrante entre diabéticos foi de 16,5%. Não encontramos correlação entre as variáveis sociodemográficas (sexo, idade, tempo de DM, escolaridade e renda familiar) e a ocorrência de ITB aberrante.

Abstract Background The ankle-brachial index (ABI) is a screening test for peripheral arterial occlusive disease and it can also be used to assess cardiovascular risk. However, in diabetics it can be difficult to interpret because the index may be excessively high because of calcification of the arterial tunica media. Objective To determine the frequency of high ABI in diabetics and to test for associations with sociodemographic variables. Methods This was a descriptive study in which 309 type 2 diabetes patients were interviewed and had their ABI measured. The sample was recruited at a referral center for diabetes and endocrinology (CEDEBA) in Salvador, BA, Brazil. The frequency of excessively high ABI and its relationships with sociodemographic variables such as sex, age and family income were studied. The cutoff point chosen for excessively high ABI was 1.3. Continuous variables were dichotomized. The chi-square test was used for statistical analysis and results with p ≤ 0.05 were considered significant. Results A total of 309 patients were interviewed, 65% were women, 26% had graduated from secondary education and 77% had a family income equal to or less than three times the minimum salary. The frequency of excessively high ABI (≥ 1.3) was 16.5%. Bivariate analyses detected no statistically significant correlations between excessively high ABI (≥ 1.3) and the sociodemographic variables studied (sex, age, time since diagnosis of diabetes mellitus, family income and educational level). Conclusions The frequency of high ABI among this sample of diabetics was 16.5%. We did not detect correlations between the sociodemographic variables (sex, age, duration of DM, educational level and family income) and high ABI.

Formas graves de retinopatia predizem aterosclerose subclínica em indivíduos com diabetes tipo 1 / Severe forms of retinopathy predict the presence of subclinical atherosclerosis in type 1 diabetes subjects

FUNDAMENTO: Em pacientes com diabetes tipo 2, a presença de retinopatia está associada a doença cardiovascular aumentada, independentemente dos fatores de risco conhecidos para a doença vascular. OBJETIVO: Investigar a associação da retinopatia diabética (RD) e seus graus com a presença de aterosclerose coronariana subclínica em pacientes com diabetes tipo 1. MÉTODOS: Um estudo transversal foi conduzido com 150 pacientes com diabetes tipo 1, assintomáticos para doença arterial coronariana. Foram submetidos à avaliação clínica para verificar complicações microvasculares e avaliação para a presença de calcificação arterial coronariana (CAC). RESULTADOS: Formas graves de RD (RD grave não proliferativa - RDNP - e RD proliferativa - RDP) foram associadas à CAC (RC: 3,98; IC de 95 por cento; 1,13-13,9, p = 0,03), de maneira independente dos fatores de risco conhecidos para a doença cardiovascular (idade, A1C, hipertensão, dislipidemia e sexo masculino). CONCLUSÃO: Os pacientes com formas graves de RD estão em risco de presença de doença arterial coronariana, de maneira independente dos tradicionais fatores de risco cardiovascular.

BACKGROUND: In patients with type 2 diabetes, the presence of retinopathy is associated with increased cardiovascular disease, regardless of known risk factors for vascular disease. OBJECTIVE: To investigate the association of diabetic retinopathy (DR) and its grades with the presence of subclinical coronary atherosclerosis in patients with type 1 diabetes. METHODS: A cross-sectional study was conducted with 150 type 1 diabetes individuals asymptomatic for coronary artery disease. They underwent clinical evaluation for microvascular complications and for the presence of coronary artery calcification (CAC). RESULTS: Severe forms of DR (severe non-proliferative DR and proliferative DR) were associated with CAC (OR: 3.98 95 percent CI 1.13-13.9, p = 0.03), regardless of known risk factors for cardiovascular disease (age, A1C, hypertension, dyslipidemia and male gender). CONCLUSION: Patients with severe forms of DR are at risk for the presence of coronary artery disease regardless of traditional cardiovascular risk factors.