T.J. Palao Garcia
- Small arteries, big problems
- New insights in the mechanisms of small artery remodeling in hypertension
E.T. van Bavel
- Award date
- 2 November 2018
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
Small artery remodeling consists of changes in the amount or arrangement of vessel wall components, resulting in changes in lumen diameter and/or wall thickness. This process is associated with hypertension, but its underlying mechanisms are not fully understood. The objective of this thesis was to obtain new insights into the mechanisms of small artery remodeling.
In the first part of this work we have provided with a list of miRNA´s and mRNA´s differentially expressed in small arteries from hypertensive rats. From this list, we further focused on thrombospondin-4 (TSP-4), as it was the most upregulated gene in hypertensive small arteries. For this purpose, we used thrombospondin 4 knockout animals, infused with angiotensin II as a model for hypertension. The data presented in different chapters from this thesis suggest an important role for TSP-4 in the remodeling found in hypertension across the cardiovascular system, including the heart, aorta, and resistance arteries.
In the second part of the thesis we have presented a novel setup for the study of conducted vasoactive responses and demonstrated the existence of sustained conducted vasomotor responses in small arteries. This work provides a basis for studies on functional and structural adaptations along arteries in microvascular networks. In conclusion, the research presented in this thesis has contributed to new insights on the pathophysiological mechanisms of small artery remodeling, providing directions for further research in the field.
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