Abstract 353: Mast Cell Inhibition Attenuates Cardiac Remodeling and Diastolic Dysfunction in Ovariectomized Female Fischer344хBrown Norway Rats
Background: The incidence of left ventricular hypertrophy (LVH) and diastolic dysfunction (LVDD) increases in postmenopausal women, but no proven pharmacologic interventions exist. Mast cells have an important role in the pathological processes of a variety of cardiac diseases. We determined the cardioprotective effects of chronic mast cell inhibition by the mast cell stabilizer, cromolyn sodium, in middle-aged, female Fischer344хBrown Norway (F344BN) rats after estrogen (E2) loss.
Methods and Results: Bilateral ovariectomy (OVX) or sham-operations were performed in 18-month-old female F344BN rats. Four weeks after surgery, cromolyn (30 mg/kg/day), or vehicle (saline) was administered s.c. by osmotic minipump (n=7/group). Four weeks after treatment, systolic blood pressure (SBP) increased by 20% in OVX vs. sham rats, and cromolyn attenuated this effect. Myocardial relaxation (e’) was reduced (P<0.01), left ventricle (LV) filling pressures (E/e’) were increased (P<0.01), and LV mass, wall thicknesses, and percent interstitial fibrosis were increased in OVX vs. sham rats. All of these adverse effects of E2 loss on LV function and structure were mitigated by cromolyn treatment. While no differences in plasma angiotensin (Ang) II levels were observed between OVX and sham, Ang II levels were reduced in cromolyn-treated OVX rats (P<0.05). Cardiac chymase protein expression was increased after E2 loss, irrespective of cromolyn. Yet, treatment with cromolyn prevented the increase in cardiac Ang II type 1 receptor (AT1aR) mRNA expression with OVX.
Conclusions: Mast cell inhibition with cromolyn attenuates adverse LV remodeling and LVDD in OVX-F344BN rats possibly through a chymase/Ang II-mediated mechanism. Cardiac mast cells could be a potential therapeutic target for cardiovascular diseases in postmenopausal women.
Author Disclosures: H. Wang: None. J. da Silva: None. A. Alencar: None. M. Lin: None. X. Sun: None. L. Groban: 2. Research Grant; Significant; NIH AG-042758 (LG), NIH AG-033727 (LG).
- © 2015 by American Heart Association, Inc.