Atherosclerosis of aorta
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Atherosclerosis of the Aorta: Insights and Implications
Introduction to Aortic Atherosclerosis
Atherosclerosis of the aorta is a chronic inflammatory condition characterized by the thickening and hardening of the arterial wall due to plaque buildup. This condition can lead to severe cardiovascular complications, including stroke, myocardial infarction, and peripheral artery disease. Understanding the predictors, mechanisms, and management strategies for aortic atherosclerosis is crucial for improving patient outcomes.
Predictors of Neurologic Events and Mortality
Ascending Aorta Atherosclerosis as a Predictor
Atherosclerosis of the ascending aorta has been identified as an independent predictor of long-term neurologic events and mortality. A study involving 1,957 patients undergoing cardiac surgery found that the severity of atherosclerosis in the ascending aorta significantly increased the risk of neurologic events and all-cause mortality. Specifically, the incidence of these events increased more than threefold as the severity of atherosclerosis progressed from mild to severe.
Topography and Stroke Risk
The topography of aortic atherosclerosis also plays a critical role in predicting stroke risk. Patients with atherosclerosis in the distal part and lesser curvature of the ascending aorta exhibited a significantly higher risk of stroke post-cardiac surgery. The five-year stroke-free survival rate was markedly lower in patients with extensive aortic disease compared to those without.
Mechanisms and Pathophysiology
Metabolic and Inflammatory Changes
Metabolic profiling of atherosclerotic aortic tissue has revealed significant alterations in oxidative stress and inflammation pathways. Dysregulation in purine and glutathione pathways, along with increased levels of inflammatory markers such as glucosylceramide and quinic acid, were observed in plaque-containing aortic tissues. These metabolic changes highlight the complex interplay between oxidative stress and inflammation in the pathogenesis of atherosclerosis.
Autoimmune Reactions
Atherosclerosis may also involve autoimmune mechanisms. Studies on cadaveric aortic tissues have shown infiltration of lymphocytes, plasma cells, and increased levels of interleukin-17 (IL-17) in the aortic wall. These findings suggest that autoimmune reactions contribute to the inflammatory processes underlying atherosclerosis .
DNA Methylation and Gene Expression
Alterations in DNA methylation patterns in vascular smooth muscle cells (SMCs) are associated with atherosclerosis. Hypermethylated regions in aorta-associated enhancer chromatin were linked to genes involved in SMC function and atherosclerosis, such as ACTA2 and MYH11. These epigenetic changes may facilitate the phenotypic modulation of SMCs, promoting a pro-atherosclerotic environment.
Management Strategies
Surgical Interventions
Severe atherosclerosis of the ascending aorta and aortic arch poses significant challenges during cardiac surgery. Replacement of the atherosclerotic aorta, often involving deep hypothermic circulatory arrest, has been shown to be a viable strategy to mitigate the risk of systemic embolism and improve survival rates. Despite the associated perioperative morbidity, this approach can significantly reduce the expected rates of death and stroke.
Murine Models for Research
Murine models, particularly LDL receptor-deficient and apolipoprotein E-deficient mice, have been instrumental in studying atherosclerosis. These models exhibit extensive aortic lesions and provide valuable insights into the pathological factors driving lesion formation. The correlation between lesion extent in the aortic origin and the entire aorta underscores the utility of these models in atherosclerosis research.
Conclusion
Atherosclerosis of the aorta is a multifaceted disease with significant implications for neurologic events and mortality. Understanding the predictors, underlying mechanisms, and effective management strategies is essential for improving patient outcomes. Continued research, particularly in the areas of metabolic profiling, autoimmune mechanisms, and epigenetic changes, will further elucidate the complexities of aortic atherosclerosis and pave the way for innovative therapeutic approaches.
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