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Lung ACE is Not Involved in The Progression of Pulmonary Arterial Hypertension
Author(s) -
Joshi Sachindra,
Gupte Sachin
Publication year - 2015
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.29.1_supplement.662.9
Subject(s) - medicine , hypoxia (environmental) , lung , right ventricular hypertrophy , pulmonary hypertension , pulmonary artery , cardiology , hypoxic pulmonary vasoconstriction , muscle hypertrophy , pathology , chemistry , oxygen , organic chemistry
Rationale Although ACE–Ang II–AT1R axis has been well documented in promoting vasoconstriction, proliferation, and fibrosis‐the hallmarks of pulmonary arterial hypertension (PAH), the role of lung ACE in the progression of PAH is not clear. Pharmacological inhibition of ACE to effectively attenuate the progression of PAH has been ambiguous. Therefore, we sought to determine if knocking out lung ACE would prevent the progression of PAH. Methods To test this hypothesis we evaluated development of PAH in ACE knock‐out (ACE.3) and wild type C57BL mice using Sugen 5416‐Hypoxia PAH model. Wild type and ACE knock‐out mice were exposed to 3 weeks of normoxia or chronic hypoxia and simultaneously administered the sugen 5416 at 0, 1, and 3 weeks. Pulmonary artery acceleration time (PAAT) was measured by transthoracic echocardiography on week 0 and week 3. Right ventricular hypertrophy was assessed by taking the RV/LV+S weight. Cardiac function was assessed by left heart catheterization using Millar 1.4 F catheter. Pulmonary arteriopathy was assessed from hematoxylin and eosin stained formalin fixed paraffin embedded lung sections. Results Significant decrease in PAAT in sugen hypoxia wild type and ACE knock‐out compared to vehicle or sugen normoxia control was similar. The degree of right ventricular hypertrophy in sugen hypoxia ACE knock‐out and wild type was not different. Decreased cardiac output between sugen hypoxia wild type and the ACE knock‐out was similar. The arteriopathy in sugen hypoxia wild type and ACE knock‐out were also similar, which included medial thickening, occlusive lesions and plexiform‐like lesions. Conclusion It appears that lung ACE may not be involved in the progression of the PAH.