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DIMINISHED SERUM ARYLESTERASE ACTIVITY LEVELS IN PULMONARY HYPERTENSION SECONDARY TO LEFT HEART DISEASE IS NOT RELATED TO DYSREGULATED ARGININE METHYLATION.
E1613 JACC March 27, 2012 Volume 59, Issue 13
Pulmonary Hypertension DIMINISHED SERUM ARYLESTERASE ACTIVITY LEVELS IN PULMONARY HYPERTENSION SECONDARY TO LEFT HEART DISEASE IS NOT RELATED TO DYSREGULATED ARGININE METHYLATION. ACC Moderated Poster Contributions McCormick Place South, Hall A Sunday, March 25, 2012, 11:00 a.m.-Noon
Session Title: Pulmonary Hypertension: Epidemiology and Risk Factors Abstract Category: 30. Pulmonary Hypertension Presentation Number: 1132-609 Authors: Yenal Harper, David Kennedy, Earl Britt, Wai Hong Tang, Cleveland Clinic Foundation, Cleveland, OH, USA Background: Studies have shown that diminished serum arylesterase level is associated with states of high oxidative stress. It is used as a marker of diminishing antioxidant capabilities and as an independent factor in predicting adverse cardiac outcomes. Paraoxonase (PON), an HDL associated protein thought to mediate some of the atheroprotective functions of HDL, catalyzes endogenous serum arylesterase activity Nitric oxide (NO) is a potent endothelium-derived vasorelaxant produced from arginine via NO synthases, which can be inhibited by dysregulated methylated products of arginine such as symmetric dimethylarginine (SDMA). Decreased nitric oxide may lead to defective endothelial functionality and repair. We aimed to look at the relationship between arylesterase methylated arginine products and pulmonary pressures in patients with heart failure and pulmonary arterial hypertension, and Endothelial progenitor cell proliferation. Methods: We prospectively collected blood samples at the level of the pulmonary artery from 30 consecutive patients with advanced heart failure undergoing right heart catheterization. We measured serum arylesterase levels. Plasma metabolites of arginine metabolism and serum arylesterase levels were analyzed using mass and UV spectrophotometry respectively. Results: In our study cohort (mean age 58±15 years, 63% male, 83% Caucasian,(median mPAP 33 mmHg interquartile range (IQR) [22-43] mmHg, and PCWP 14 IQR [19-25] mmHg). 66% had evidence of pulmonary hypertension . The median arylesterase levels were 92 IQR [72-112] uM. Patients with pulmonary hypertension ( mPAP > 25mmHG) had significantly lower arylesterase levels than those with lower mPAP, 86 IQR [70-98] vs. 113 IQR [74-137] respectively, p=0.021. Also Patients with heart failure and a mPAP >25mm HG had higher levels of SDMA than those with lower pressures 18 IQR [6-10] vs 11 IQR [6-10] respectively. p=0.012 Conclusion: Patients with PH have lower HDL-associated PON-1 activity as measured by aryl, and is independent of dysregulated arginine metabolism.
Pulmonary Hypertension DIMINISHED SERUM ARYLESTERASE ACTIVITY LEVELS IN PULMONARY HYPERTENSION SECONDARY TO LEFT HEART DISEASE IS NOT RELATED TO DYSREGULATED ARGININE METHYLATION. ACC Moderated Poster Contributions McCormick Place South, Hall A Sunday, March 25, 2012, 11:00 a.m.-Noon
Session Title: Pulmonary Hypertension: Epidemiology and Risk Factors Abstract Category: 30. Pulmonary Hypertension Presentation Number: 1132-609 Authors: Yenal Harper, David Kennedy, Earl Britt, Wai Hong Tang, Cleveland Clinic Foundation, Cleveland, OH, USA Background: Studies have shown that diminished serum arylesterase level is associated with states of high oxidative stress. It is used as a marker of diminishing antioxidant capabilities and as an independent factor in predicting adverse cardiac outcomes. Paraoxonase (PON), an HDL associated protein thought to mediate some of the atheroprotective functions of HDL, catalyzes endogenous serum arylesterase activity Nitric oxide (NO) is a potent endothelium-derived vasorelaxant produced from arginine via NO synthases, which can be inhibited by dysregulated methylated products of arginine such as symmetric dimethylarginine (SDMA). Decreased nitric oxide may lead to defective endothelial functionality and repair. We aimed to look at the relationship between arylesterase methylated arginine products and pulmonary pressures in patients with heart failure and pulmonary arterial hypertension, and Endothelial progenitor cell proliferation. Methods: We prospectively collected blood samples at the level of the pulmonary artery from 30 consecutive patients with advanced heart failure undergoing right heart catheterization. We measured serum arylesterase levels. Plasma metabolites of arginine metabolism and serum arylesterase levels were analyzed using mass and UV spectrophotometry respectively. Results: In our study cohort (mean age 58±15 years, 63% male, 83% Caucasian,(median mPAP 33 mmHg interquartile range (IQR) [22-43] mmHg, and PCWP 14 IQR [19-25] mmHg). 66% had evidence of pulmonary hypertension . The median arylesterase levels were 92 IQR [72-112] uM. Patients with pulmonary hypertension ( mPAP > 25mmHG) had significantly lower arylesterase levels than those with lower mPAP, 86 IQR [70-98] vs. 113 IQR [74-137] respectively, p=0.021. Also Patients with heart failure and a mPAP >25mm HG had higher levels of SDMA than those with lower pressures 18 IQR [6-10] vs 11 IQR [6-10] respectively. p=0.012 Conclusion: Patients with PH have lower HDL-associated PON-1 activity as measured by aryl, and is independent of dysregulated arginine metabolism.