Molecular Pharmacological Approaches for Treating Abdominal Aortic Aneurysm

Abstract

Abdominal aortic aneurysm (AAA) is considered to be a potent life-threatening disorder in elderly individuals. Although many patients with a small AAA are detected during routine abdominal screening, there is no effective therapeutic option to prevent the progression or regression of AAA in the clinical setting. Recent advances in molecular biology have led to the identification of several important molecules, including microRNA and transcription factor, in the process of AAA formation. Regulation of these factors using nucleic acid drugs is expected to be a novel therapeutic option for AAA. Nucleic acid drugs can bind to target factors, mRNA, microRNA, and transcription factors in a sequence-specific fashion, resulting in a loss of function of the target molecule at the transcriptional or posttranscriptional level. Of note, inhibition of a transcription factor using a decoy strategy effectively suppresses experimental AAA formation, by regulating the expression of several genes associated with the disease progression. This review focuses on recent advances in molecular therapy of using nucleic acid drugs to treat AAA.

AAA Revisited: A Comprehensive Review of Risk Factors, Management, and Hallmarks of Pathogenesis

“…Future perspectives of pharmacological approaches to limit AAA growth also include nucleic acid drugs that target mRNAs, microRNAs, or transcription factors in a sequence-specific manner to interfere with key molecules in AAA pathogenesis [ 249 ].…”

A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy

“…Their efficacy on AAA formation had been confirmed in experimental studies. However, there is no evidence for beneficial in clinical trials 5 . Therefore, the treatment of small AAA remains an imperative clinical problem 6 .…”

Gene Regulatory Network Analysis of Perivascular Adipose Tissue of Abdominal Aortic Aneurysm Identifies Master Regulators of Key Pathogenetic Pathways

“…Nonetheless, our data suggest that lymphocyte activation and proliferation mechanisms could be crucial for amplifying the local antigen-driven immune response in the PVAT of AAA patients. Interfering with NK-kB signaling [ 45 ] in immune cells may, thus, have a significant impact on the evolution of AAA. Although immune-suppressive treatment should be carefully evaluated [ 46 ], selectively inhibiting NF-kB signaling in activated and proliferating lymphocytes in dysfunctional AAA PVAT may be a targeted therapeutic intervention without compromising the healthy effect mediated by NF-kB in other immune cells.…”

“…Notably, an immune phenotyping analysis in human AAA samples recently found that T-lymphocytes are the primary cell leukocyte population in AAA, with the largest concentration in PVAT, and that these PVAT-associated T-lymphocytes correlated with the severity of the disease [ 66 ]. Assessing the presence of a locally restricted, antigen-driven clonal expansion in PVAT of AAA could, thus, be the goal of future studies, which will allow for the precise detection of pathogenic lymphocytes for direct interference treatment [ 45 ], possibly through the above-suggested disease gene targets.…”