Abstract
Abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA) are serious arterial diseases in the aorta and brain, respectively. AAA and IA are associated with old age in males and females, respectively, and if rupture occurs, they carry high morbidity and mortality. Aneurysmal subarachnoid hemorrhage (SAH) due to IA rupture has a high rate of complication and fatality. Despite these severe clinical outcomes, preventing or treating these devastating diseases remains an unmet medical need. Inflammation and oxidative stress are shared pathologies of these vascular diseases. Therefore, therapeutic strategies have focused on reducing inflammation and reactive oxygen species levels. Interestingly, in response to cellular stress, the inducible heme oxygenase-1 (HO-1) is highly upregulated and protects against tissue injury. HO-1 degrades the prooxidant heme and generates molecules with antioxidative and anti-inflammatory properties, resulting in decreased oxidative stress and inflammation. Therefore, increasing HO-1 activity is an attractive option for therapy. Several HO-1 inducers have been identified and tested in animal models for preventing or alleviating AAA, IA, and SAH. However, clinical trials have shown conflicting results. Further research and the development of highly selective HO-1 regulators may be needed to prevent the initiation and progression of AAA, IA, or SAH.
Highlights
Abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA) are both arterial aneurysms, IAs are characterized by a distinct saccular morphology that is different from AAAs
Elastin fragmentation and degradation of extracellular matrix (ECM) by matrix metalloproteinases (MMPs) result in arterial wall weakening [32]. Given that both inflammation and oxidative stress contribute to AAAs and IAs, pharmacological therapeutic strategies aimed at reducing inflammation and reactive oxygen species (ROS) levels appear to be promising approaches for preventing/treating these devastating vascular diseases
Further supporting a critical role of heme oxygenase-1 (HO-1) in AAA development, we demonstrated unequivocally that Heme oxygenase (HO)-1 expression was crucial in AAA growth and severity
Summary
Cardiovascular diseases remain the leading cause of death worldwide, in developed countries. Men with advanced age are more prone to develop AAAs and male gender is associated with a four-fold higher risk of AAA [3,4,5]. AAAs and IAs are both arterial aneurysms, IAs are characterized by a distinct saccular morphology that is different from AAAs. In contrast to the male prevalence of AAAs, IAs have higher prevalence in females [10,11] and increase rapidly with age [12]. SAH is associated with a higher rate of medical complications and 40–50% mortality [16]. The estimated annual cost of SAH in the United States is USD 1.755 billion, more than three-fold higher than the costs associated with unruptured IAs [9]. Factors associated with an increased risk of aneurysm rupture include race, hypertension, cigarettes and alcohol use, and IA diameter larger than 7 mm [21,22]
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