| First Author | Palao T | Year | 2018 |
| Journal | Cardiovasc Pathol | Volume | 35 |
| Pages | 12-19 | PubMed ID | 29729633 |
| Mgi Jnum | J:345733 | Mgi Id | MGI:6850978 |
| Doi | 10.1016/j.carpath.2018.03.003 | Citation | Palao T, et al. (2018) Thrombospondin-4 mediates cardiovascular remodelling in angiotensin II-induced hypertension. Cardiovasc Pathol 35:12-19 |
| abstractText | 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. |
