ABSTRACT
The associations between hyperhomocysteinaemia (HHcy), methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and abdominal aortic aneurysm (AAA) remain controversial, with only few studies focused on these associations within the Chinese population. We performed subgroup and interaction analyses in a Chinese Han population to investigate these associations. In all, 155 AAA patients and 310 control subjects were evaluated for serum total homocysteine levels and MTHFR C677T polymorphisms. Multiple logistic regression models were used to evaluate the aforementioned associations. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and chronic disease histories. The multiple logistic analyses showed a significant association between HHcy and AAA but no significant association between MTHFR C677T polymorphism and AAA. The interaction analysis showed that age and peripheral arterial disease played an interactive role in the association between HHcy and AAA, while drinking status played an interactive role in the association between MTHFR C677T polymorphism and AAA. In conclusion, HHcy is an independent risk factor of AAA in a Chinese Han population, especially in the elderly and peripheral arterial disease subgroups. Longitudinal studies and clinical trials aimed to reduce homocysteine levels are warranted to assess the causal nature of these relationships.
Subject(s)
Aortic Aneurysm, Abdominal , Asian People , Hyperhomocysteinemia , Methylenetetrahydrofolate Reductase (NADPH2) , Polymorphism, Genetic , Aged , Aortic Aneurysm, Abdominal/blood , Aortic Aneurysm, Abdominal/ethnology , Aortic Aneurysm, Abdominal/genetics , Asian People/ethnology , Asian People/genetics , Case-Control Studies , China/ethnology , Female , Homocysteine/blood , Homocysteine/genetics , Humans , Hyperhomocysteinemia/blood , Hyperhomocysteinemia/ethnology , Hyperhomocysteinemia/genetics , Male , Methylenetetrahydrofolate Reductase (NADPH2)/blood , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Risk FactorsABSTRACT
OBJECTIVE: To examine the potential influence factors of abdominal aortic aneurysm (AAA). METHODS: A 1:2 pair-matched, case-control study was conducted from July 2011 to December 2012. A pair was composed of one AAA patient recruited from the Vascular Surgery Department, Chinese PLA General Hospital and two gender- and age-matched non-AAA subjects, one from the same hospital and the other from the community in Fangshan District in Beijing. Demographic data, medical history and the lifestyle of each subject were collected. Moreover, all the participants underwent abdominal ultrasound or computed tomography (CT) and peripheral venous blood samples were obtained. RESULTS: There were 155 case/control pairs. The multivariate conditional logistic regression model confirmed that suffering from hypertension conferred a 1.98-fold (95%CI 1.12-3.18) increased likelihood of AAA. Smoking was a strong independent risk factor of AAA, with odds ratios (95% confidence intervals) of 5.23 (2.44-11.23). Dyslipidemia (OR=2.61,95% CI 1.45-4.70), a higher level of serum hsCRP (OR=2.43,95%CI 1.37-4.31) and homocysteine (OR=2.73,95% CI 1.61-4.65) were all associated with AAA. CONCLUSION: Hypertension and smoking are the risk factors of AAA. Dyslipidemia, hsCRP and Hcy are associated with AAA.
Subject(s)
Aortic Aneurysm, Abdominal/epidemiology , Asian People , C-Reactive Protein/metabolism , Case-Control Studies , Dyslipidemias , Homocysteine/blood , Humans , Hypertension , Logistic Models , Odds Ratio , Risk Factors , Smoking , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: The pathological characteristics of abdominal aortic aneurysm (AAA) involved the regression of extracellular matrix (ECM) in aortic walls, especially elastic structure in medial layer. As the major structural protein of aorta, elastin contributes to the extensibility and elastic recoil of the vessels. We hypothesized that overexpression of elastin in vessel walls might regenerate the elastic structure of ECM, restore the elastic structure of the aneurysmal wall, and eventually lead to a reduction of aortic diameters (ADs) in an experimental model of AAA. METHODS: Tropoelastin (TE) of Sprague Dawley (SD) rat was synthesized by reverse transcription polymerase chain reaction and used to construct adneviral vectors containing elastin precursor protein (AdTE-GFP). Cultured vascular smooth muscle cells (VSMCs) from aortas of male SD rats were transfected with AdTE-GFP, AdGFP, adenoviral vector (AdNull), and phosphate buffered saline (PBS). Immunofluorescence staining was performed to determine the expression of elastin in transfected cells. The expression of elastic fibers in ECM of VSMCs transfected with AdTE-GFP were detected by fluorescence microscopy and transmission electron microscopy (TEM) at 1, 3, and 5 days following gene transfer. The AAA vessel walls were infused with AdTE-GFP or an empty AdNull, or PBS directly into the aneurysmal lumen. ADs of the aneurysms were compared in infused aortas. Formation of new elastic fibers in vivo was assessed by hematoxylin and eosin, and elastic von-Giesson staining. Recombinant elastin-GFP in vivo was identified by immunohistochemical staining. RESULTS: Elastic fibers were increased both in ECM of VSMC and in vessel walls after gene transfer. Histological studies revealed that the AdTE-GFP-transduced aortas had elastic fiber regeneration in the aneurysmal walls. The AdTE-GFP-transduced aortas showed a decreased AD (23.04% ± 14.49%, P < 0.01) in AAA vessel walls. CONCLUSIONS: Elastic fibers have been successfully overexpressed both in vitro and in a rat model of AAA by a technique of gene transfer. The overexpression of elastic fibers within the aneurysmal tissue appeared to reverse the aneurysm dilatation in this model.
