Immune Modulation as a Treatment for Abdominal Aortic Aneurysms
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In the United States, >200 000 new patients are diagnosed with abdominal aortic aneurysm (AAA) each year. Consequently, >40 000 highly morbid aortic reconstructions are performed each year to prevent aneurysm rupture, a catastrophic event associated with near-certain mortality. No pharmaceutical currently exists to slow aneurysm growth, but a 50% reduction in diameter growth per annum could halve the number of aortic reconstructions required. Therefore, successful use of cell therapy to modulate chronic inflammation hallmark to AAA to slow diameter expansion represents a potentially paradigm-altering treatment.
There continues to be no US Food and Drug–approved medication to slow or stop AAA growth. This deficit is certainly not because of a lack of effort over the previous decades. Initial investigations focused on the reduction of mechanical stress through decreasing blood pressure and sac pressurization cycles; however, clinical trials investigating drugs, such as, angiotensin II–converting enzyme inhibitors, angiotensin receptor blockers, and β-blockers, all failed to demonstrate a therapeutic reduction of diameter growth compared with placebo. Next, the inhibition of matrix metalloproteinases was trialed with doxycycline, an antibiotic inhibitor of matrix metalloproteinases 2 and 9. Doxycycline also treats species of Chlamydia, which were isolated from the aortic walls of a minority of aneurysmal arteries. Although initial uncontrolled results were promising, therapeutic response was not replicated in large randomized studies. Last, aortic wall inflammation was targeted using statins, a ubiquitous anti-inflammatory, lipid-lowering drug to limited success. The discovery of a nonsurgical treatment for AAA is contingent on the robust understanding of disease pathogenesis, which continues to be nebulous at best.
AAA risk factors, such as, tobacco abuse, advancing age, uncontrolled hypertension, male sex, and white ethnicity, have all been well described but fail to provide evidence elucidating pathogenesis. Regardless, existing evidence implicates that disease initiation is multifactorial with a strong genetic element. There has been …