Fuster, Valentin

K-Raman, Purushothaman

Kini, Annapoorna

Krishnan, Prakash

Lento, Patrick A.

Levy, Andrew P.

Mehran, Roxana

Moreno, Pedro R.

Purushothaman, Meerarani

Sharma, Samin K.

Elsevier - Publisher Connector 

E1301
JACC April 5, 2011
Volume 57, Issue 14
  QUALITY OF CARE AND OUTCOMES ASSESSMENT 
GENOTYPE-DEPENDENT IMPAIRMENT OF HEMOGLOBIN CLEARANCE INCREASES OXIDATIVE STRESS 
AND INFLAMMATION LEADING TO ACCELERATED NEOVASCULARIZATION IN HUMAN DIABETIC 
ATHEROSCLEROSIS
ACC Poster Contributions
Ernest N. Morial Convention Center, Hall F
Tuesday, April 05, 2011, 9:30 a.m.-10:45 a.m.
Session Title: Genetic Associations with Cardiovascular Phenotypes and Endophenotypes
Abstract Category: 11. Peripheral Arterial/Carotid Disease/Aortic Disease
Session-Poster Board Number: 1178-170
Authors: Meerarani Purushothaman, Purushothaman K-Raman, Prakash Krishnan, Andrew P. Levy, Patrick A. Lento, Roxana Mehran, Annapoorna 
Kini, Samin K. Sharma, Valentin Fuster, Pedro R. Moreno, Mount Sinai Medical Center, New York, NY
Background:  As we have previously reported free hemoglobin (Hb) released from intra-plaque hemorrhage (IPH) induces oxidative stress. This 
pattern may be increased in diabetes atherosclerosis with Hp 2-2 genotype. We hypothesize that impairment of hemoglobin clearance will induce 
pro-oxidative and pro-inflammatory state, leading to increased macrophage infiltration and neovascularization in human atheroma.
Methods:  Forty human DM patients with peripheral vascular disease (PVD) were genotyped using DNA isolated from blood by PCR, and their 
peripheral plaques collected simultaneously for analysis. IPH was identified using H&E stained slides. Hb clearance impairment was evaluated by 
gene expression of CD163 and HO-1. Furthermore, gene and protein expression of pro-oxidative (myeloperoxidase, MPO) marker, pro-inflammatory 
(IL-6), and anti-inflammatory (IL-10) cytokines were also evaluated. Finally, macrophage infiltration (grade 0-3) and plaque neovascularization 
(density) were quantified by immunohistochemistry.
Results:  See table and figures. 
Conclusions:  Our results indicate impaired Hb clearance, identified by decreased expression of CD163 and HO-1 pathways may lead to increased 
oxidative stress, pro-inflammatory cytokine and decreased anti-inflammatory cytokine expression were documented. Furthermore we showed that 
these events may lead to increased macrophage infiltration and accelerated neovascularization in DM atheroma from patients with Hp 2.2 genotype. 


GENOTYPE-DEPENDENT IMPAIRMENT OF HEMOGLOBIN CLEARANCE INCREASES OXIDATIVE STRESS AND INFLAMMATION LEADING TO ACCELERATED NEOVASCULARIZATION IN HUMAN DIABETIC ATHEROSCLEROSIS 

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GENOTYPE-DEPENDENT IMPAIRMENT OF HEMOGLOBIN CLEARANCE INCREASES OXIDATIVE STRESS AND INFLAMMATION LEADING TO ACCELERATED NEOVASCULARIZATION IN HUMAN DIABETIC ATHEROSCLEROSIS

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