Abstract P165: Hypertension Increases Susceptibility To Experimental Malaria In Mice

Abstract

Despite available treatments, global prevalence of hypertension is on the rise and burdening healthcare, especially in under-developed countries where infectious diseases are also rampant. Previously we reported that hypertension is associated with abnormal red blood cell (RBC) physiology and anemia. Since RBCs are target host cells for malarial pathogen, Plasmodium , we hypothesized that hypertensive patients with abnormal RBC physiology are at an increased risk of susceptibility to Plasmodial infection. Methods: To test this hypothesis, eight weeks old hypertensive BPH/2J and normotensive BPN/3J female mice (n=6) were first characterized for their RBC physiology and subsequently infected with Plasmodium yoelii (P. yoelii) , a murine-specific non-lethal strain. Results: Compared to BPN mice, BPH mice displayed comparable RBC count, but lower hemoglobin (BPH 16.3±0.8, vs BPN 16.5±1.0 mg/dL; p<0.01); lower % hematocrit (BPH 59.6 ±2.4 vs BPN 61.0 ± 2.7; p<0.01), and lower mean corpuscular volume (BPH 52.6±3.13 vs BPN 54.2±1.6 fl; p<0.005), indicating microcystic anemia. Further, RBCs from BPH mice were resistant to osmotic hemolysis in hypotonic (0.42%) NaCl solution (% hemolysis BPH 43.2±1.6% vs 97.3±1.8% BPN; p<0.001). Lower membrane fluidity was observed in the RBCs of BPH mice as noted through higher levels of the saturated fatty acid, stearate (BPH 16.2±0.1% vs BPN 13.9±0.16%; p<0.001), phospholipids (BPH 554±18.3 vs BPN 496±6.2 μg/mg protein p=0.02) and lower polyunsaturated fatty acids like arachidonic acid (BPH 13.7±0.1% vs BPN 15.1±0.5%, BPN; p=0.03). Further, upon infection for 7 days with P. yoelii , BPH mice experienced severe body weight loss compared to minimal change in body weight noted in the BPN mice (BPH Day 0 18.53±0.32 g vs Day 7 16.43±0.71 g vs BPN Day 0 22.5±1.28 g vs Day 7 22.43±1.30 g; p<0.01). This was accompanied by a significantly decreased number of RBC compared to BPN mice (BPH 3.4±1.3х10 12 vs BPN 5.5±1.2х10 12 cells/L; p=0.03), indicating that BPH mice were more susceptible to malaria infection. Conclusion: Collectively, these data demonstrate that aberrant RBC physiology observed in hypertensive mice contributes to an increased susceptibility to experimental malaria.