(P01-052-20) A Polyphenol Rich Muscadine Grape Extract Reduces Macrophage Infiltration in Hypertensive Rat Hearts Associated with a Reduction in Macrophage Migration

Objectives: Hypertension affects over a billion people world-wide and is a major risk factor for cardiovascular disease.  Macrophages, the most abundant innate immune cells, home to the heart and secrete cytokines, inducing a heightened inflammatory response which results in fibrosis and cardiac damage.  Muscadine grapes are rich in polyphenols, compounds with anti-proliferative, anti-fibrotic, and anti-inflammatory properties.  Our aim was to determine whether a muscadine grape extract (MGE) rich in polyphenols prevents the macrophage inflammatory response induced by hypertension.

Methods: A proprietary extract was prepared from muscadine grape seeds and skins.  Male Sprague-Dawley rats (8 weeks old) received drinking water (control), MGE at 0.2 mg total phenolics/ mL, 24 μg/kg/h of angiotensin II (Ang II) via osmotic minipump to induce hypertension, or both Ang II and MGE (Ang II/MGE) for 4 weeks.  Rats were pre-treated with MGE for 1 week prior to Ang II treatment.  Blood pressure was measured weekly by tail cuff plethysmography. Tissues were collected and fixed for immunohistochemistry.  Proliferation and migration of macrophage-like RAW264.7 cells were quantified in real-time.

Results: MGE had no effect on blood pressure in normotensive or hypertensive rats.  MGE ameliorated Ang II-induced diastolic dysfunction (E/E’ ratio: 19.9±0.8 control, 28.1±1.1 Ang II, 22.3±2.0 Ang II/MGE rats; n=8; p < 0.05), interstitial cardiac fibrosis (p< 0.05) and collagen III deposition (0.9±0.2% Control, 6.8±1.0% Ang II, 2.8±0.4% Ang II/MGE; p< 0.01).  Thus, MGE may improve diastolic dysfunction in part through a reduction in pathological fibrosis.  Ang II caused a significant increase in CD68-positive macrophages in cardiac tissue, which was blocked by MGE (% positive cells/field: control 6.1±0.4, Ang II 12.5±2.0, Ang II/MGE 5.4±0.5, p< 0.01).  Treatment of RAW264.6 cells with MGE (20 µg/mL total phenolics) for 18 h attenuated stimulated cell migration by 2-fold with no effect on proliferation (n=3, p< 0.5), indicating that MGE may reduce the Ang II-mediated increase in cardiac macrophages by blocking migration.

Conclusions: MGE may serve as medical food to protect the heart from hypertension-induced inflammation thereby reducing cardiac fibrosis to improve diastolic dysfunction.

Funding Sources: Chronic Disease Research Fund