RESUMO
Aortic diseases such as atherosclerosis, aortic aneurysms, and aortic stiffening are significant complications that can have significant impact on end-stage cardiovascular disease. With limited pharmacological therapeutic strategies that target the structural changes in the aorta, surgical intervention remains the only option for some patients with these diseases. Although there have been significant contributions to our understanding of the cellular architecture of the diseased aorta, particularly in the context of atherosclerosis, furthering our insight into the cellular drivers of disease is required. The major cell types of the aorta are well defined; however, the advent of single-cell RNA sequencing provides unrivaled insights into the cellular heterogeneity of each aortic cell type and the inferred biological processes associated with each cell in health and disease. This review discusses previous concepts that have now been enhanced with recent advances made by single-cell RNA sequencing with a focus on aortic cellular heterogeneity.
Assuntos
Doenças da Aorta , Aterosclerose , Humanos , RNA , Aorta/metabolismo , Doenças da Aorta/genética , Perfilação da Expressão Gênica , Aterosclerose/genética , Aterosclerose/metabolismoRESUMO
Hypertension is a major risk factor for both stroke and cognitive impairment, but it is unclear whether it may specifically affect post-stroke cognitive impairment. We assessed the effect of hypertension and/or stroke on brain injury, cognitive outcome, and the brain transcriptomic profile. C57BL/6J mice (n = 117; 3-5 mo.) received s.c. infusion of either saline or angiotensin II followed by sham surgery or photothrombotic stroke targeting the prefrontal cortex seven days later. Cognitive function was assessed with the Barnes maze and RNA sequencing was used to quantify transcriptomic changes in the brain. Angiotensin II treatment produced spontaneous hemorrhaging after stroke. In the Barnes maze, hypertensive mice that received stroke surgery had an increased escape latency compared to other groups (day 3: hypertensive + stroke = 166.6 ± 6.0 s vs. hypertensive + sham = 122.8 ± 13.8 s vs. normotensive + stroke = 139.9 ± 10.1 s vs. normotensive + sham = 101.9 ± 16.7 s), consistent with impaired cognition. RNA sequencing revealed >1500 differentially expressed genes related to neuroinflammation in hypertensive + stroke vs. normotensive + stroke, which included genes associated with apoptosis, microRNAs, autophagy, anti-cognitive biomarkers and Wnt signaling. Overall, we show that the combination of hypertension and stroke resulted in greater learning impairment and brain injury.