The Role of Inflammation and Myeloperoxidase-Related Oxidative Stress in the Pathogenesis of Genetically Triggered Thoracic Aortic Aneurysms.
Cassandra MaleckiBrett D HamblyRichmond W JeremyElizabeth N RobertsonPublished in: International journal of molecular sciences (2020)
Genetically triggered thoracic aortic aneurysms (TAAs) are usually considered to exhibit minimal levels of inflammation. However, emerging data demonstrate that specific features of an inflammatory response can be observed in TAA, and that the extent of the inflammatory response can be correlated with the severity, in both mouse models and in human studies. Myeloperoxidase (MPO) is a key mediator of the inflammatory response, via production of specific oxidative species, e.g., the hypohalous acids. Specific tissue modifications, mediated by hypohalous acids, have been documented in multiple cardiovascular pathologies, including atherosclerosis associated with coronary artery disease, abdominal aortic, and cerebral aneurysms. Similarly, data are now emerging that show the capacity of MPO-derived oxidative species to regulate mechanisms important in TAA pathogenesis, including alterations in extracellular matrix homeostasis, activation of matrix metalloproteinases, induction of endothelial dysfunction and vascular smooth muscle cell phenotypic switching, and activation of ERK1/2 signaling. The weight of evidence supports a role for inflammation in exacerbating the severity of TAA progression, expanding our understanding of the pathogenesis of TAA, identifying potential biomarkers for early detection of TAA, monitoring severity and progression, and for defining potential novel therapeutic targets.
Keyphrases
- inflammatory response
- oxidative stress
- extracellular matrix
- smooth muscle
- lipopolysaccharide induced
- lps induced
- coronary artery disease
- toll like receptor
- abdominal aortic
- mouse model
- electronic health record
- spinal cord
- endothelial cells
- aortic valve
- left ventricular
- diabetic rats
- dna damage
- cardiovascular disease
- single cell
- stem cells
- big data
- pulmonary artery
- cell therapy
- body mass index
- cell proliferation
- weight loss
- physical activity
- heart failure
- subarachnoid hemorrhage
- bone marrow
- type diabetes
- percutaneous coronary intervention
- brain injury
- genetic diversity
- pulmonary arterial hypertension
- coronary artery bypass grafting
- acute coronary syndrome
- aortic dissection
- heat shock
- immune response
- cerebral ischemia
- pluripotent stem cells