Glucose Intolerance Is Associated with Increased Intimal Medial Thickness of the Carotid Artery and Increased Pulse Wave Velocity in Renal Transplant Recipients

Uchida, J.; Machida, Yuichi; Iwai, Tomohiro; Kuwabara, N.; Kabei, Kazuya; Kumada, Norihiko; Nakatani, Takeshi

doi:10.1097/00007890-201211271-00583

Cited by 3 publications

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“…Among nonclassic risk factors, CRP (9) and biomarkers of CKD-MBD (10) undergo dramatic changes after transplantation, and FGF23 and 1,25(OH) 2 vitamin levels approach the normal range in most patients, whereas serum PTH often remains mildly to moderately elevated (27). Numerous low-powered cross-sectional ultrasound studies of carotid arteries have been performed in patients with renal transplants (28)(29)(30)(31)(32). The vast majority of these studies considered isolated biomarkers (mainly biomarkers of inflammation) (29,31,32) or just a limited set of purported risk factors.…”

Section: Discussionmentioning

confidence: 99%

A Longitudinal Study of Inflammation, CKD-Mineral Bone Disorder, and Carotid Atherosclerosis after Renal Transplantation

Yılmaz

Sönmez

Sağlam

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives The role of reversibility of nontraditional risk factors, like inflammation and CKDmineral bone disorder, in the reduction of cardiovascular risk after renal transplantation is still scarcely defined.Design, setting, participants, and measurements The longitudinal relationship between C-reactive protein, CKDmineral bone disorder biomarkers, and intima media thickness was investigated in a series of 178 patients (age=32610 years) with stage 5 CKD maintained on chronic dialysis who underwent echo-color Doppler studies of the carotid arteries before and after renal transplantation. Smokers and patients with diabetes were excluded from the study. In all patients, immunosuppression was performed by a standard regimen on the basis of calcineurin inhibitors. Healthy controls were specifically selected to match the age and sex distribution of the patients. Biochemical and intima media thickness assessments were repeated 6 months after transplantation.Results Before transplantation, intima media thickness in patients with stage 5 CKD on dialysis (average=0.960.2 mm) was higher (P,0.001) than in well matched healthy controls (0.660.1 mm) and reduced substantially (222%; 95% confidence interval, 224% to 220%) after transplantation (P=0.001). GFR (multivariable-adjusted b=0.23; P,0.001), C-reactive protein (b=0.15; P,0.001), and fibroblast growth factor 23 (b=0.28; P,0.001) were the strongest independent correlates of intima media thickness before transplantation. Similarly, longitudinal changes in the same biomarkers were the sole independent correlates of simultaneous changes in intima media thickness (C-reactive protein: b=0.25; fibroblast growth factor 23: b=0.26; P,0.001 for both) after renal transplantation. The evolution of intima media thickness after transplantation was largely independent of classic risk factors, including BP, LDL cholesterol, and insulin resistance, as measured by homeostatic model assessment.Conclusions Intima media thickness improves after renal transplantation. Such an improvement associates with parallel changes in serum C-reactive protein and fibroblast growth factor 23. These observations are in keeping with the hypothesis that the decline in cardiovascular risk after transplantation, in part, depends on partial resolution of nontraditional cardiovascular risk factors, like inflammation and CKD-mineral bone disorder.

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Section: Discussionmentioning

confidence: 99%

A Longitudinal Study of Inflammation, CKD-Mineral Bone Disorder, and Carotid Atherosclerosis after Renal Transplantation

Yılmaz

Sönmez

Sağlam

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…This condition is characterized by excessive fibrosis and progressive loss of elasticity of central and conduit arteries, leading to reduced arterial storage capacity as well as increasing the speed of the propagating pulse along the vessel wall. 4,5 A high-fat diet is considered to be a major cause of MetS; however, cholesterol-lowering therapy with statins has a moderate effect on the stiffness of large conduit arteries. 6 Hence, clarification of the molecular mechanism of metabolic disorder–induced arterial stiffness as well as the identification of new therapeutic targets are urgently required.…”

mentioning

confidence: 99%

Yes-Associated Protein Targets the Transforming Growth Factor β Pathway to Mediate High-Fat/High-Sucrose Diet-induced Arterial Stiffness

Liu

et al. 2022

Circulation Research

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Background: Metabolic syndrome is related to cardiovascular diseases, which is attributed in part, to arterial stiffness; however, the mechanisms remain unclear. The present study aimed to investigate the molecular mechanisms of metabolic syndrome–induced arterial stiffness and to identify new therapeutic targets. Methods: Arterial stiffness was induced by high-fat/high-sucrose diet in mice, which was quantified by Doppler ultrasound. Four-dimensional label-free quantitative proteomic analysis, affinity purification and mass spectrometry, and immunoprecipitation and GST pull-down experiments were performed to explore the mechanism of YAP (Yes-associated protein)-mediated TGF (transforming growth factor) β pathway activation. Results: YAP protein was upregulated in the aortic tunica media of mice fed a high-fat/high-sucrose diet for 2 weeks and precedes arterial stiffness. Smooth muscle cell–specific YAP knockdown attenuated high-fat/high-sucrose diet–induced arterial stiffness and activation of TGFβ-Smad2/3 signaling pathway in arteries. By contrast, Myh11Cre ERT2 -Yap Tg mice exhibited exacerbated high-fat/high-sucrose diet–induced arterial stiffness and enhanced TGFβ-activated Smad2/3 phosphorylation in arteries. PPM1B (protein phosphatase, Mg 2+ /Mn 2+ -dependent 1B) was identified as a YAP-bound phosphatase that translocates into the nucleus to dephosphorylate Smads in response to TGFβ. This process was inhibited by YAP through removal of the K63-linked ubiquitin chain of PPM1B at K326. Conclusions: This study provides a new mechanism by which smooth muscle cell YAP regulates the TGFβ pathway and a potential therapeutic target in metabolic syndrome–associated arterial stiffness.

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“…Conversely, several epidemiological and experimental studies suggest that cardio-vascular anomalies could foster the development of type 2 diabetes: patients who suffer from hypertension, myocardial infarction, or arterial stiffness as measured by the carotid-femoral pulse wave velocity [2][3][4], and patients who smoke [5,6] are all more at risk of type 2 diabetes than control subjects or than non-smoker patients. Patients with an increased carotid intima-media thickness, a marker of cardio-vascular risk, are more frequently glucose intolerant [7,8]. Moreover, in the NAVIGATOR study that included patients with impaired glucose tolerance and cardiovascular disease or risk factors, treatment with an angiotensin II receptor antagonist for 5 years decreased the incidence of diabetes [9].…”

Section: Introductionmentioning

confidence: 99%

Patients with type 2 diabetes present with multiple anomalies of the pancreatic arterial tree on abdominal computed tomography: comparison between patients with type 2 diabetes and a matched control group

Alexandre‐Heymann

Barral

Dohan

et al. 2020

Cardiovasc Diabetol

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Background: Studies suggest that cardio-vascular risk factors could foster the development of type 2 diabetes (T2D). This could partly be mediated by pancreatic atherosclerosis resulting in pancreatic ischemia. We hypothesized that patients with T2D present with more severe atherosclerosis of pancreas-bound arteries than control patients without T2D. Methods: We performed a retrospective study comparing the abdominal computed tomography of patients with T2D and of control subjects matched for gender and for age. We performed a multivariate logistic regression with adjustment for age, gender, BMI and the presence or absence of hypertension. Results: Forty-eight patients with T2D and 48 control subjects were included. A calcification score of the splenic artery was defined (from 0: no calcification to 3: continuous linear calcifications). Seventeen percent of the patients with T2D presented with a high calcification score (i.e. 2 or 3), versus only 2% of the control subjects (p = 0.04). The mean number of pancreas-bound branches among the greater pancreatic artery, dorsal pancreatic artery and inferior pancreatic artery (from 0 to 3) was lower in patients with T2D than in control subjects (1.1 vs 1.7, p = 0.003). The mean number of visible intrapancreatic arterial subdivisions (from 0 to 2) was lower in patients with T2D than in control subjects (0.7 vs 1.3, p = 0.0017). All these differences hold true using multivariate logistic regression. None of these differences correlated with the duration of diabetes. The relationship between pancreas volume and BMI seen in control subjects was not confirmed in patients with T2D. Conversely, in patients with T2D but not in control subjects, the splenic artery diameter correlated with the pancreas volume. Conclusions: Patients with T2D present with more calcifications of the splenic artery and with a less dense pancreatic arterial tree than control subjects.

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Glucose Intolerance Is Associated with Increased Intimal Medial Thickness of the Carotid Artery and Increased Pulse Wave Velocity in Renal Transplant Recipients

Cited by 3 publications

References 0 publications

A Longitudinal Study of Inflammation, CKD-Mineral Bone Disorder, and Carotid Atherosclerosis after Renal Transplantation

A Longitudinal Study of Inflammation, CKD-Mineral Bone Disorder, and Carotid Atherosclerosis after Renal Transplantation

Yes-Associated Protein Targets the Transforming Growth Factor β Pathway to Mediate High-Fat/High-Sucrose Diet-induced Arterial Stiffness

Patients with type 2 diabetes present with multiple anomalies of the pancreatic arterial tree on abdominal computed tomography: comparison between patients with type 2 diabetes and a matched control group

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