TY - JOUR
T1 - Thrombospondin-4 mediates cardiovascular remodelling in angiotensin II-induced hypertension
AU - Palao, Teresa
AU - Medzikovic, Lejla
AU - Rippe, Catarina
AU - Wanga, Shaynah
AU - Al-Mardini, Claudia
AU - van Weert, Angela
AU - de Vos, Judith
AU - van der Wel, Nicole N.
AU - van Veen, Henk A.
AU - van Bavel, Ed T.
AU - Swärd, Karl
AU - de Waard, Vivian
AU - Bakker, Erik N. TP
PY - 2018
Y1 - 2018
N2 - Thrombospondin 4 (TSP-4) expression is induced in the heart and vasculature under pathological conditions, including myocardial infarction, myocardial pressure overload, and hypertension. TSP-4 is linked to remodelling processes, where it may affect extracellular matrix protein organization. In previous work, we studied the role of TSP-4 in small arteries during hypertension using Ang II-treated Thrombospondin 4 knockout (Thbs4−/−) mice. We reported increased heart weight, as well as the occurrence of aortic aneurysms in the Ang II-treated Thbs4−/− animals. In the present study, we further characterized the hearts and aortas from these animals. Hypertrophy of cardiomyocytes, together with perivascular fibrosis and inflammation was observed in the Ang II-treated Thbs4−/− hearts. In the aortas, an increase in the aortic wall cross-sectional area (CSA) and wall thickness of the Ang II-treated Thbs4−/− mice was found. More detailed investigation of the Ang II-treated Thbs4−/− aortas also revealed the appearance of aortic dissections in the outer medial layer of the arteries, as well as pronounced inflammation. No differences were found in several other extracellular matrix-related parameters, such as number of elastin breaks or stress–strain relationships. However, at the ultrastructural level, collagen fibers showed alterations in diameter in the media and adventitia of the Ang II-treated Thbs4−/− mice, in the area prone to dissection. In conclusion, we identified TSP-4 as an important protein in the development of cardiac hypertrophy and aortic dissections in Ang II-induced hypertension.
AB - Thrombospondin 4 (TSP-4) expression is induced in the heart and vasculature under pathological conditions, including myocardial infarction, myocardial pressure overload, and hypertension. TSP-4 is linked to remodelling processes, where it may affect extracellular matrix protein organization. In previous work, we studied the role of TSP-4 in small arteries during hypertension using Ang II-treated Thrombospondin 4 knockout (Thbs4−/−) mice. We reported increased heart weight, as well as the occurrence of aortic aneurysms in the Ang II-treated Thbs4−/− animals. In the present study, we further characterized the hearts and aortas from these animals. Hypertrophy of cardiomyocytes, together with perivascular fibrosis and inflammation was observed in the Ang II-treated Thbs4−/− hearts. In the aortas, an increase in the aortic wall cross-sectional area (CSA) and wall thickness of the Ang II-treated Thbs4−/− mice was found. More detailed investigation of the Ang II-treated Thbs4−/− aortas also revealed the appearance of aortic dissections in the outer medial layer of the arteries, as well as pronounced inflammation. No differences were found in several other extracellular matrix-related parameters, such as number of elastin breaks or stress–strain relationships. However, at the ultrastructural level, collagen fibers showed alterations in diameter in the media and adventitia of the Ang II-treated Thbs4−/− mice, in the area prone to dissection. In conclusion, we identified TSP-4 as an important protein in the development of cardiac hypertrophy and aortic dissections in Ang II-induced hypertension.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85046790264&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29729633
U2 - https://doi.org/10.1016/j.carpath.2018.03.003
DO - https://doi.org/10.1016/j.carpath.2018.03.003
M3 - Article
C2 - 29729633
SN - 1054-8807
VL - 35
SP - 12
EP - 19
JO - Cardiovascular pathology
JF - Cardiovascular pathology
ER -