Premium
The role of inflammation and adaptive immunity in aortic stiffening
Author(s) -
WU JING,
Thabet Salim,
Chen Wei,
Goldstein Anna,
Madhur Meena,
Hudson Billy,
Harrison David
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1133.5
Subject(s) - elastin , angiotensin ii , inflammation , chemistry , adventitia , medicine , endocrinology , fibrosis , masson's trichrome stain , elastase , hydroxyproline , pathology , blood pressure , biochemistry , enzyme
Clinical studies show an association between inflammation and arterial stiffness. We have previously demonstrated that T lymphocytes mediate experimental hypertension and vascular dysfunction in various models. In addition, T cells‐derived pro‐inflammatory cytokines such as IL‐17 and TGF‐β are known to induce fibrosis. We therefore propose that hypertensive stimuli induce T cell activation and the secretion of cytokines promote aortic stiffening in hypertension. Using masson trichrome staining, we initially observed profound collagen deposition in the aortic adventitia in C57Bl/6J mice receiving chronic angiotensin II infusion (490ng/kg/min, 14 days). We then biochemically determined the alteration of ECM proteins using hydroxyproline assay and ninhydrin assay. Angiotensin II treatment significantly increased collagen content in the aortas of C57Bl/6J mice by more than two fold (1.3±0.1 μg/mm v.s. 3.5 ±0.3 μg/mm, p<0.01) and this increase was further amplified in Recombination Activating Gene‐1 knockout (Rag1−/−) mice lacking mature lymphocytes (1.3±0.2 μg/mm v.s. 5.6±0.8 μg/mm, p<0.01). Although elastin content was not reduced, the elastin to collagen ratio was significantly depressed by angiotensin II infusion in both strains (23.4±1.2 v.s. 9.5±0.9, p<0.01; 25.5±3.5 v.s. 7.5±0.9, p<0.01). Consistently, angiotensin II increased aortic wall thickness (p<0.01), media to lumen ratio (p<0.01) while decreased extensibility index (p<0.01) in C57Bl/6J mice. These changes in pathology and mechanical properties were less impressive in Rag1−/− mice (p<0.01 for all three parameters). Collectively, our data demonstrate that arterial stiffening might be caused by alteration in ECM proteins, vascular hypertrophy and loss of elasticity. There is clearly an involvement of inflammation and adaptive immunity in the pathogenesis of aortic stiffening.