Abstract 9013: Fibrinogen Related Homologous C-terminus Peptides (haptides) Modulate Systemic Blood Preasure By Mast Cells Activation
Introduction: A family of short peptides (“Haptides”) homologous to C-termini sequences of fibrinogen chains β and γ (Cβ and preCγ) were previously shown to bind and penetrate cells.
Hypothesis: We suggest that haptides may affect the cardiovascular system.
Methods: Haptides effect on systemic blood pressure (BP) was tested in a rat model by an intra-arterial monitor and in-vitro by activation of both human LAD2 and rat peritoneal mast cells.
Results: IV administration of Haptides in rats caused a sharp transient dose dependent drop of the systolic and diastolic BP by up to 55% (p<0.05), with minor heart rate increase (Fig. 1, A-D). Randomly scrambled Haptides had no effect. IV administration of histamine receptor blockers before Haptides attenuated this effect which seems to be related to mast cells activation. Haptides induced mast cells degranulation was also demonstrated with human LAD2 cell line and isolated rat peritoneal mast cells (Fig. 1, E-F).
In conclusion: Haptides activate mast cells to release histamine. This results in a steep decrease in BP. Vascular occlusive diseases are treated by intensive degradation of fibrin which release haptide containing sequences; therefore, we suggest that histamine receptor blockers or other mast cell stabilizing agents in such pathological conditions may overcome this effect.
Fig. 1: Haptides reduce rat blood-pressure in a dose dependent manner by mast cell activation Records of arterial BP at baseline and 6 min after injection into the femoral veins of 2 mg/kg of the Haptide Cβ. The rats were injected with escalating doses (35, 70, 140, 280 & 560 μg/kg/ animal) of Haptides or Cα (n=6). Efffect of Haptides on: (A) diastolic, (B) Systolic, (C)MAP: Main arterial BP, (D) HR. E-F: Effect of Haptides on β-hex release by human LAD2 mast cells. 2×105 cells/ml were preincubated for 2 min (E) or 30 min (F) with 50 or 100μg/ml Haptides or with the control peptide (n=4). Results presented as % of maximum of β-hex release. *p<0.05, ** p<0.01
- © 2010 by American Heart Association, Inc.