Plasma Levels Of Cathepsins, Cytokines And Risks Of Abdominal Aortic Aneurysms:a Randomized Population-based Study

Part I Plasma levels of cathepsins L, K, and V and risks of abdominal aortic aneurysms:A randomized population-based studyObjective:Cathepsin L (CatL), cathepsin K (CatK), and cathepsin V (CatV) are potent elastases implicated in human arterial wall remodeling. Whether plasma levels of these cathepsins are altered in patients with abdominal aortic aneurysms (AAAs) remains unknown.Methods:Plasma samples were collected from 476 male AAA patients and 200 age-matched male controls to determine CatL, CatK, and CatV levels by ELISA. Student's t-test and ROC curve analysis demonstrated the significance between AAA patients and controls. Pearson's correlation test demonstrated the association between CatL and potential confounders. Multivariate logistic regression analysis proved that whether CatL act as a risk factor of AAA before and after the same confounder adjustment.Results:Student's t-test demonstrated significantly higher plasma CatL levels in AAA patients than in controls (P< 0.0001), whereas CatK and CatV levels were lower in AAA patients than in controls (P=0.052, P=0.025). ROC curve analysis confirmed higher plasma CatL levels in AAA patients than in controls (P< 0.001). As potential confounders, current smoking and use of angiotensin-converting enzyme (ACE) inhibitors, aspirin, clopidogrel, and statins associated with significantly increased plasma CatL. Pearson's correlation test demonstrated that plasma CatL associated positively with CatS (r=0.43, P< 0.0001), body-mass index (BMI) (r=0.07, P=0.047) and maximal aortic diameter (r=0.29, P< 0.001), and negatively with lowest measured ankle-brachial index (ABI) (r=0.22, P< 0.001). Plasma CatL remained associated positively with CatS (r=0.43, P< 0.0001) and aortic diameter (r=0.212, P< 0.001) and negatively with ABI (r=0.10, P=0.011) after adjusting for the aforementioned potential confounders in a partial correlation analysis. Multivariate logistic regression analysis indicated that plasma CatL was a risk factor of AAA before (odds ratio [OR]=3.04, P< 0.001) and after (OR=2.42, P< 0.001) the same confounder adjustment.Conclusions:Correlation of plasma CatL levels with aortic diameter and the lowest ABI suggest that this cysteinyl proteaseplays a detrimental role in the pathogenesis of human peripheral arterial diseases and AAAs.Part II Plasma cytokine levels and risks of abdominal aortic aneurysms:A population-based prospective cohort studyObjective:Abdominal aortic aneurysm (AAA) is characterized by inflammatory cell accumulation in AAA lesions that produce inflammatory cytokines and advance its pathogenesis. Peripheral cytokines may predict the degree or risk of AAA.Methods:ELISA determined plasma interleukin-6 (IL6), IL10, IL17A, IFN-y, and C-reactive protein (CRP) from 476 AAA patients and 200 controls.Results:AAA patients had lower IL6, IFN-y, IL10, IL17A, and higher CRP than controls. IL10 correlated positively with IFN-y, IL17A, or IL6, but not CRP in control or AAA populations. IL10 associated negatively with systolic blood pressure, whereas CRP associated positively with diastolic blood pressure and body mass index. CRP was an independent AAA risk factor and correlated positively with aortic diameters before and after adjustments for other risk factors. IFN-y, IL17A, and CRP correlated positively with cross-sectional AAA area after adjustment. IL10 correlated positively with AAA growth rate before and after adjustment. AAA patients with CRP levels above the median doubled the risk of death.Conclusions:Reduced IFN-y, IL10, and IL17A in AAA patients, positive correlations of IFN-Y and IL17A with cross-sectional AAA area, IL10 with AAA growth rate, and IL10 with IFN-y and IL17A suggest combined Thl, Th2, and Th17 immune responses in human AAAs.