Autoantibodies to Oxidized Low-Density Lipoprotein in Patients with Aortic Regurgitation: Association with Aortic Diameter Size

Abstract

Background: Aortic regurgitation (AR) is a condition associated with volume overload, causing left-ventricular (LV) remodeling, eccentric LV hypertrophy and eventually heart failure. LV remodeling associated with AR is regulated by mechanical stress, neurohormonal activation, inflammation and oxidative stress. Since anti-oxidized low-density lipoprotein (LDL) antibodies (Abs) are a measurable marker of oxidative stress, we hypothesized that an increased level of circulating oxidized LDL (oxLDL) Abs may be related to remodeling of the left ventricle in patients with significant AR. Methods: We assessed IgG anti-oxLDL Abs in 31 patients with significant AR and compared them to 30 patients with similar risk factors and no valvular disease. Abs to oxLDL were determined by ELISA. Results: The 2 groups had similar clinical characteristics. There was no difference between patients with AR and patients with no AR in the level of anti-oxLDL Abs. However, in all patients and controls, anti-oxLDL Abs correlated positively with the diameter of the ascending aorta (AA; r = 0.32, p = 0.016) and the level of oxLDL Abs was significantly higher in patients with an AA diameter ≥39 mm. On multivariate analysis, only white blood cell count and AA diameter were related to anti-oxLDL Abs in all patients. Conclusions: We did not find a difference in the level of anti-oxLDL Abs between patients with AR and controls; however, there was a strong correlation between anti-oxLDL Abs and AA diameter.

Are oxidised low-density lipoproteins the true inducers of inflammation in atherosclerosis?

“…A local loss of this tolerance can induce a local response after the recognition of apoB protein as an autoantigen and consequently complicate the lesion [135][136][137]. A low number of patients develop specific IgG against ox-LDL whereas others do it against carbamilated and glycosilated proteins [138][139][140]; the presence of these specific antibodies is an important individual complication in the evolution of lesions in some patients. Thus, there are a high number of factors that could contribute with ox-LDL in complicating an atheroma with different tendencies and each patient has their own set of risk factors that complicate their disease.…”

Circulating Autoantibodies to Oxidized Low-Density Lipoprotein in Patients with Ascending Aortic Aneurysms: Marker of Oxidative Stress Involved in Pathogenesis, Epiphenomenon of Endothelial Dysfunction, or Pure Chance?

“…As a matter of fact, the correlation of anti-oxLDL Abs with AAD, as reported by Shimoni et al [4], was an incidental finding resulting from post hoc analysis of the original data. This correlation essentially relates only to patients with AR, as there were only 3 patients with dilated aortas in the control group, and, when these were removed from the analysis, the difference in anti-oxLDL Abs between patients with dilated and nondilated aortas was amplified.…”

“…This might reasonably explain why, when only patients with AR were included in the analysis, the association of anti-oxLDL Abs and AAD was more pronounced. A follow-up study, specifically designed and powered to replicate the intriguing ‘hypothesis-generating' findings reported by Shimoni et al [4], will be eagerly anticipated.…”

“…Hence, one would expect a negative or nonexistent association of ATAAs with atherosclerotic markers. Intriguingly, in the latest issue of Cardiology, Shimoni et al [4] report a strong positive correlation between the ascending aorta diameter (AAD) and a marker of oxidative stress reportedly correlating with atherosclerosis, namely IgG autoantibodies to oxidized low-density lipoprotein (anti-oxLDL Abs). …”

Usefulness of Antibodies to Oxidized Low-Density Lipoproteins as Predictors of Morbidity and Prognosis in Heart Failure Patients Aged ≥65 Years

“…Those antibodies have already been shown to correlate with the extent of atherosclerosis and to predict future myocardial infarction. [15][16][17][18][19][20][21] Oxidative stress has been reported to increase in subjects aged 65 years and older, possibly arising from an uncontrolled production of free radicals by ageing mitochondria and decreased antioxidant defenses. 7,9,10,[12][13][14][15][16][17][18][19][20][21][22][23][24] The aim of this study was to assess the potential applicability of OxLDLAb levels in predicting morbidity, mortality and the composite outcome of the two in a cohort of patients with chronic HF who were 65 years of age and older.…”