Correlation between cathepsin D serum concentration and carotid intima-media thickness in hemodialysis patients

Moallem, Seyed Adel; Nazemian, Fatemeh; Eliasi, Sepideh; Alamdaran, Seyed Ali; Shamsara, Jamal; Mohammadpour, Amir Hooshang

doi:10.1007/s11255-010-9729-4

Cited by 21 publications

(21 citation statements)

References 30 publications

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“…Especially among newly diagnosed type 2 diabetic patients, cathepsin D were strongly correlated with insulin resistance. In agreement with previous finding [ 12 ], our data indicate that circulating cathepsin D levels associate positively with triglyceride levels in all participants.…”

Section: Discussionsupporting

confidence: 93%

“…Although cathepsin D has been implicated in acidic milieu of lysosomes with important consequences in regulation of apoptosis, it represents an important prognostic factor in a variety of cancers and is therefore considered to be a potential important molecule and influences cell signaling [ 10 ]. Previous studies have suggested that cathepsin D plays an important role in cholesterol trafficking and atherosclerosis [ 11 , 12 ]. Cathepsin D has been proposed as a biomarker for nonalcoholic steatohepatitis [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Increased Cathepsin D Correlates with Clinical Parameters in Newly Diagnosed Type 2 Diabetes

et al. 2017

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Background Cathepsin D has been recently implicated in insulin resistance and cardiovascular disease. This study was designed to investigate the relationship between cathepsin D and newly diagnosed type 2 diabetes. Methods Circulating cathepsin D levels and metabolic variables were measured in 98 cases and 98 controls. Myocardial performance index “Tei index” that reflects both left ventricular systolic and diastolic function was measured with Doppler echocardiography in cases. Results Newly diagnosed type 2 diabetes demonstrated significantly higher circulating cathepsin D concentrations than controls (median level: 227 ng/ml versus 174 ng/ml, P < 0.01). In newly diagnosed type 2 diabetes, a significant correlation was found between cathepsin D levels and HOMA-IR (homeostatic model assessment of insulin resistance) (r = 0.25, P = 0.01). In contrast, no significant correlation was found between cathepsin D levels and clinical parameters in the control group (all P > 0.05). Interestingly, correlation analysis revealed a positive association between cathepsin D levels and Tei index in type 2 diabetes (r = 0.22, P = 0.03). Conclusions Increased levels of circulating cathepsin D are closely linked with the presence of type 2 diabetes, and cathepsin D might serve as a novel biomarker for cardiac dysfunction in newly diagnosed type 2 diabetes.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Increased Cathepsin D Correlates with Clinical Parameters in Newly Diagnosed Type 2 Diabetes

et al. 2017

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“…Furthermore, we have recently reported that plasma CatD was strongly associated with pediatric NASH11. Likewise, a correlation exists between CatD and carotid intima-media thickness, an indicator for atherosclerosis49, as well as with a lysosomal storage disease50, diseases which both are predominantly characterized by chronic systemic inflammation and excessive cholesterol storage inside macrophages. In line, in the current paper, we show that CatD is correlated with histological classifications for NASH as well as with cholesterol.…”

Section: Discussionmentioning

confidence: 94%

Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

Walenbergh

Houben

Rensen

et al. 2016

Sci Rep

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Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from children due to a different histological pattern in the liver. Yet, the link between plasma CatD to adult NASH was not examined. In the current manuscript, we investigated whether plasma CatD in adults correlates with NASH development and regression. Biopsies were histologically evaluated for inflammation and NAFLD in three complementary cohorts of adults (total n = 248). CatD and alanine aminotransferase (ALT) were measured in plasma. Opposite to our previous observations with childhood NASH, we observed increased levels of plasma CatD in patients with NASH compared to adults without hepatic inflammation. Furthermore, after surgical intervention, we found a reduction of plasma CatD compared to baseline. Our observations highlight a distinct pathophysiology between NASH in children and adults. The observation that plasma CatD correlated with NASH development and regression is promising for NASH diagnosis.

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“…For examples, decreased myocardial CTSD protein levels in human dilated cardiomyopathy (DCM) and increased plasma levels of CTSD in patients with acute coronary syndrome were reported; 32, 33 furthermore, a higher level of serum CTSD was associated with atherogenesis, 34 increased risk of coronary events, 35 carotid intima-media thickness, 36 and endothelial dysfunction. 37 However, important questions regarding how CTSD deficiency affects cardiac function and whether the altered myocardial CTSD expression plays an important role in cardiac pathogenesis remain unanswered.…”

mentioning

confidence: 99%

Myocardial Upregulation of Cathepsin D by Ischemic Heart Disease Promotes Autophagic Flux and Protects Against Cardiac Remodeling and Heart Failure

Yuan

et al. 2017

Circ: Heart Failure

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Background Lysosomal dysfunction is implicated in human heart failure for which ischemic heart disease is the leading cause. Altered myocardial expression of cathepsin D (CTSD), a major lysosomal protease, was observed in human heart failure but its pathophysiological significance has not been determined. Methods and Results Western blot analyses revealed an increase in the precursor but not the mature form of CTSD in myocardial samples from explanted human failing hearts with ischemic heart disease, which is recapitulated in chronic myocardial infarction produced via coronary artery ligation in Ctsd+/+ but not Ctsd+/− mice. Mice deficient of Ctsd displayed impaired myocardial autophagosome removal, reduced autophagic flux, and restrictive cardiomyopathy. After induction of myocardial infarction, weekly serial echocardiography detected earlier occurrence of left ventricle chamber dilatation, greater decreases in ejection fraction and fractional shortening, and lesser wall thickening throughout the first 4 weeks; pressure-volume relationship analyses at 4-week revealed greater decreases in systolic and diastolic functions, stroke work, stroke volume, and cardiac output; greater increases in the ventricular weight to body weight and the lung weight to body weight ratios and larger scar size were also detected in Ctsd+/− mice compared with Ctsd+/+ mice. Significant increases of myocardial autophagic flux detected at 1 and 4 weeks after induction of myocardial infarction in the Ctsd+/+ mice were diminished in the Ctsd+/− mice. Conclusions Myocardial CTSD upregulation induced by myocardial infarction protects against cardiac remodeling and malfunction, which is at least in part through promoting myocardial autophagic flux.

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Correlation between cathepsin D serum concentration and carotid intima-media thickness in hemodialysis patients

Abstract: Based on the results of this study, cathepsin D could be suggested to have a role in the development of atherosclerotic plaques.

Cited by 21 publications

References 30 publications

Increased Cathepsin D Correlates with Clinical Parameters in Newly Diagnosed Type 2 Diabetes

Increased Cathepsin D Correlates with Clinical Parameters in Newly Diagnosed Type 2 Diabetes

Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

Myocardial Upregulation of Cathepsin D by Ischemic Heart Disease Promotes Autophagic Flux and Protects Against Cardiac Remodeling and Heart Failure

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