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Heme oxygenase system and hypertension: a comprehensive insight
Shuchita Tiwari, Joseph Fomusi Ndisang1
1Department of Physiology, University of Saskatchewan College of Medicine, 107 Wiggins Road, Saskatoon, SK, Canada S7N 5E5. joseph.ndisang@usask.ca.
Current Pharmaceutical Design
|August 28, 2013
Summary
Potentiating the heme oxygenase (HO) system, including its products like bilirubin and carbon monoxide, offers a promising therapeutic strategy for managing hypertension and its cardiovascular complications. This approach aims to enhance cytoprotection beyond transient physiological responses.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Pharmacology
Background:
- Hypertension is a primary global risk factor for cardiovascular disease, characterized by vascular inflammation, remodeling, and oxidative stress.
- The heme oxygenase (HO) system is activated by cellular insults but its physiological response is often insufficient to counteract hypertension's pathological effects.
- Dysregulation of HO activity is linked to hypertension and associated conditions like myocardial infarction and heart failure.
Purpose of the Study:
- To review the functional significance of the heme oxygenase (HO) system in cardiovascular physiology and pathophysiology.
- To explore the therapeutic potential of potentiating the HO system and its downstream signaling molecules for hypertension management.
- To highlight alternative therapeutic strategies targeting the HO system for hypertension and related cardiometabolic conditions.
Main Methods:
- Literature review focusing on the heme oxygenase (HO) system's role in hypertension.
- Analysis of HO system's downstream signaling pathways, including soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP).
- Examination of therapeutic agents and gene delivery methods for HO system potentiation.
Main Results:
- The HO system, through its products (carbon monoxide, bilirubin/biliverdin, ferritin), modulates cellular homeostasis and regulates blood vessel tone.
- Pharmacological potentiation or gene delivery of the HO system is necessary to overcome the threshold for effective cytoprotection in hypertension.
- HO system activation counteracts oxidative stress and inflammation, key features of hypertensive pathophysiology.
Conclusions:
- The HO system and its catabolic products represent a significant therapeutic target for hypertension.
- Enhancing HO system activity offers a novel strategy to manage hypertension and prevent associated cardiovascular complications.
- Further research into HO system potentiation could lead to effective treatments for hypertension and related cardiometabolic diseases.
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