Heme oxygenase-1 is induced in endothelial cells of newly formed vessels in chronically damaged rat livers

Abstract Kaposi sarcoma (KS) is the most common AIDS-associated malignancy and is characterized by angiogenesis and the presence of spindle cells. Kaposi sarcoma-associated herpesvirus (KSHV) is consistently associated with all clinical forms of KS, and in vitro infection of dermal microvascular endothelial cells (DMVECs) with KSHV recapitulates many of the features of KS, including transformation, spindle cell proliferation, and angiogenesis. To study the molecular mechanisms of KSHV pathogenesis, we compared the protein expression profiles of KSHV-infected and uninfected DMVECs. This comparison revealed that heme oxygenase-1 (HO-1), the inducible enzyme responsible for the rate-limiting step in heme catabolism, was up-regulated in infected endothelial cells. Recent evidence suggests that the products of heme catabolism have important roles in endothelial cell biology, including apoptosis and angiogenesis. Here we show that HO-1 mRNA and protein are up-regulated in KSHV-infected cultures. Comparison of oral and cutaneous AIDS-KS tissues with normal tissues revealed that HO-1 mRNA and protein were also up-regulated in vivo. Increased HO-1 enzymatic activity in vitro enhanced proliferation of KSHV-infected DMVECs in the presence of free heme. Treatment with the HO-1 inhibitor chromium mesoporphyrin IX abolished heme-induced proliferation. These data suggest that HO-1 is a potential therapeutic target for KS that warrants further study. (Blood. 2004;103: 3465-3473)

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Abstract 386: Body Mass Index Exacerbates the Hypertension Mediated Increase in Endothelial Cell Sloughing and Suppression of Antioxidant Heme Oxygenase-1

Hypertension ◽

10.1161/hyp.62.suppl_1.a386 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Ryan Stone ◽

David Chaffin ◽

David Jude ◽

Zeid Khitan ◽

Dong Hyun Kim ◽

...

Keyword(s):

Endothelial Cells ◽

Inflammatory Cytokines ◽

Heme Oxygenase ◽

Vascular Function ◽

Circulating Endothelial Cells ◽

Heme Oxygenase 1 ◽

Diabetic Patients ◽

Obese Patients ◽

Contributing Factors ◽

Hypertensive Patients

Introduction: Endothelial Progenitor cells (EPCs) are bone marrow derived cells that migrate and differentiate into mature endothelial cells and play a significant role in the re-endothelialization and neovascularization of injured endothelium and restoration of vascular function. We examined whether obesity and hypertension exacerbates the levels of biomarkers including circulating endothelial cells (CEC), serum inflammatory cytokines, and the levels of heme oxygenase -1 (HO-1) in EPC. Methods: Peripheral blood from 10 normal, 15 obese, 12 hypertensive, 20 obese-hypertensive and 15 diabetic patients was analyzed for inflammatory cytokines, CEC number, adiponectin and HO-1 levels. Results: The levels of inflammatory cytokines increased with BMI and directly correlated with increasing obesity. Similarly, hypertensive patients have elevated CEC which are further increased in obese hypertensive patients (p<.05). HO-1 was reduced (p<.05) in both hypertensive and obese patients when compared to control. Similarly serum adiponectin levels were lower in hypertensive obese patients when compared to controls (p<.01). Inflammatory cytokines IL-1, IL-6, MCP-1 and TNFα were elevated in obese hypertensive patients compared to non-obese hypertensive patients (p<.05). Conclusion: We demonstrated in hypertension patients that obesity exacerbates vascular dysfunction and increases circulating endothelial cells and inflammatory cytokines. A reduction in the levels of HO-1 and adiponectin imply reduced antioxidant levels which are contributing factors towards vascular and adipocyte dysfunction in hypertension patients. Thus upregulation of HO-1 offers a potential therapeutic approach in the treatment of this population.

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