ABSTRACT
Systemic VEGF inhibition disrupts endothelial homeostasis and accelerates the atherogenesis, suggesting that these events contribute to the clinical cardiovascular adverse events of VEGF-inhibiting therapies. The objective of the current study was to analyze the effect of anti-VEGF therapy on cardiovascular risk factors in patients with exudative age related macular degeneration. A total of 73 patients with exudative age related macular degeneration (without previous anti-VEGF therapy) were treated with two anti-VEGF: Ranibizumab and Pegaptanib sodium. The follow up was 6 months. The following parameters were determined before and after treatment: homocysteine, lipids (total cholesterol, triglycerides, HDL-c, LDL-c), C-Reactive Protein and fibrinogen. There were not statistically significant differences in parameters studied before and after treatment with both Pegaptanib sodium and Ranibizumab, except C-Reactive Protein. Of all patients analyzed, only 3 of them have initially C-Reactive Protein levels above normal levels and after antiangiogenic therapy, there was a significant increase in C-Reactive Protein. We have not found results in our study who to suspect that treatment with anti-VEGF in the patients with exudative age related macular degeneration increases cardiovascular risk predictors. However, after therapy was increased the CRP and fibrinogen may mean that anti-VEGF contribute an alteration of endothelial homeostasis in exudative AMD.
Subject(s)
Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Aptamers, Nucleotide/adverse effects , Biomarkers/analysis , Cardiovascular Diseases/blood , Macular Degeneration/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Aged , Aged, 80 and over , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Aptamers, Nucleotide/therapeutic use , Atherosclerosis/chemically induced , C-Reactive Protein/analysis , Cardiovascular Diseases/metabolism , Female , Fibrinogen/analysis , Homocysteine/analysis , Homocysteine/metabolism , Humans , Lipids/blood , Macular Degeneration/blood , Male , Middle Aged , Ranibizumab , Risk Factors , Wet Macular Degeneration/blood , Wet Macular Degeneration/drug therapyABSTRACT
UNLABELLED: Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment and blindness among persons aged 60 years and older and many theories exist and feature mechanisms of oxidative stress, atherosclerotic-like changes, genetic predisposition, and inflammation in development of AMD. The aim of this study was to evaluate the association between markers of inflammation and cardiovascular risk with age-related macular degeneration. METHODS: Case-control study that includes 163 patients with wet AMD (age group of 55-82 years with the mean age of 71 years and 170 age-matched healthy controls in the age group of 55-78 years with the mean age of 71 years. The following parameters were determined: lipidic profile (Total Cholesterol, Triglycerides, HDL-c, LDL-c), CRP (C-Reactive Protein), homocysteine and fibrinogen. RESULTS: We found significant differences between AMD patients and control group in baseline values of homocysteine, CRP and fibrinogen, although we do not observed differences in levels of lipidic profile. CONCLUSION: Our data support the role of chronic inflammation in the development of AMD, however, further studies are needed to determine which common disease mechanisms of chronic inflammation and atherosclerosis contribute to the pathogenesis of AMD.
Subject(s)
Biomarkers/metabolism , Cardiovascular Diseases/etiology , Macular Degeneration/complications , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Oxidative Stress , Risk FactorsABSTRACT
BACKGROUND: Lipocalin 2 (LCN2) has been related to obesity, insulin resistance and metabolic disturbance. However, its relation with non alcoholic fatty liver disease (NAFLD) has hardly been studied. METHODS: We examined LCN2 circulating levels and its protein and gene expression in liver from women with severe obesity and NAFLD. We analyzed the liver histology of 59 white severely obese women (BMI ≥40 Kg/m²): 15 subjects presented normal liver histology or non-significant liver disease (NL), 18 simple steatosis (SS) and 26 non alcoholic steatohepatitis (NASH). We determined the anthropometric and metabolic features of the women. LCN2 levels were determined by an ELISA and liver mRNA expression by real time RT-PCR. We also studied LCN2 expression in HepG2 liver cells under various inflammatory stimuli. RESULTS: Liver LCN2 protein and gene expression were higher in NAFLD than in obese with NL. Liver LCN2 gene expression correlated with SS (r=0.351, p=0.016), and its protein expression correlated with NASH (r=0.705, p=0.003). LCN2 expression was detected in HepG2 cells after the administration of TNFα, IL6, resistin or adiponectin. LCN2 expression was induced by TNFα, IL6 and resistin. CONCLUSIONS: Liver LCN2 is related to NAFLD in severely obese women. Up-regulation of LCN2 expression is detected in HepG2 cells after exposure to TNFα, IL6 and resistin. These results suggest that LCN2 expression is induced under liver harmful conditions.