Vasculotide TFA is a blood-brain barrier (BBB)-penetrant Tie2 agonist. Vasculotide TFA binds to a unique domain of Tie2, induces receptor clustering to drive phosphorylation, activates downstream PI3K/Akt and eNOS pathways, enhances inter-endothelial cell junctions (such as VE-cadherin and claudin-5 ), and inhibits inflammatory adhesion molecules, ultimately stabilizing the vascular endothelial barrier and reducing its permeability. Vasculotide TFA alleviates pulmonary microvascular leakage and microcirculatory dysfunction caused by cardiopulmonary bypass, acts as an adjuvant radioprotective agent to reduce acute radiation dermatitis, and promotes BBB recovery after focused ultrasound (FUS). Combination of Vasculotide TFA with antibiotics reduces lung injury [1] [2] [3] [4].
In Vivo, Vasculotide (200 ng per rat; intravenous injection; single dose) TFA preserves microcirculatory perfusion and reduces pulmonary vascular leakage in male Wistar rats during and after cardiopulmonary bypass, without altering the endogenous angiopoietin/Tie2 system[1]. Vasculotide (10 μg/kg; intraperitoneal injection; administered 24 h and 1.5 h prior to irradiation, followed by once every other day for 28 consecutive days) TFA reduces acute cutaneous radiation injury in mice, as evidenced by a 43% reduction in the total area of severe desquamation wounds, alleviated inflammatory responses, and improved wound healing[2]. Vasculotide (10 μg/kg; i.p.; pre-irradiation only, continuous administration, post-irradiation only; total 26 days) TFA reduces acute cutaneous radiation injury in mice exposed to 35 Gy irradiation when administered via all tested regimens (pre-irradiation, continuous administration, post-irradiation) TFA, among which the post-irradiation regimen significantly decreases the overall skin injury score by 28%[2]. Vasculotide (250 ng; intraperitoneal injection; once every 48 hours; for 3 months) TFA reduces the superharmonic threshold pressure for focused ultrasound (FUS)-induced blood-brain barrier (BBB) permeability by 21-29% in TgCRND8 mice and accelerates BBB repair, with an 87% BBB closure rate observed 20 hours after FUS treatment in this Alzheimer's disease model[3]. Adjuvant therapy with Vasculotide (500 ng; intravenous injection; 2 administrations) TFA combined with Ampicillin significantly reduces pulmonary permeability, ventilator-induced lung injury (VILI)-related histological damage and edema formation in mice with mechanically ventilated Streptococcus pneumoniae pneumonia, without affecting immune responses or bacterial loads[4].
In Vitro, Vasculotide (28 ng/mL; 3 h) TFA enhances the clonogenic survival rate of irradiated HMVEChTERT cells, with a significant SER value of 1.17[2]. Vasculotide (28 ng/mL; 3 h) TFA preserves the angiogenic capacity of HMVEChTERTs exposed to 4 Gy irradiation, resulting in the formation of tubules comparable to those of non-irradiated cells[2]. Vasculotide (15 min) TFA stimulates the phosphorylation of Tie2 receptors in HMVEChTERTs and activates the downstream AKT pro-survival pathway[2].
References:
[1]. Dekker NAM, et al. Vasculotide, an angiopoietin-1 mimetic, reduces pulmonary vascular leakage and preserves microcirculatory perfusion during cardiopulmonary bypass in rats. Br J Anaesth. 2018;121(5):1041-1051.
[2]. Korpela E, et al. Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model. BMC Cancer. 2014;14:614. Published 2014 Aug 26.
[3]. Lynch M, et al. Vasculotide restores the blood-brain barrier after focused ultrasound-induced permeability in a mouse model of Alzheimer's disease. Int J Med Sci. 2021;18(2):482-493. Published 2021 Jan 1.
[4]. Lask A, et al. Adjunctive therapy with the Tie2 agonist Vasculotide reduces pulmonary permeability in Streptococcus pneumoniae infected and mechanically ventilated mice. Sci Rep. 2022;12(1):15531. Published 2022 Sep 15.
In Vivo, Vasculotide (200 ng per rat; intravenous injection; single dose) TFA preserves microcirculatory perfusion and reduces pulmonary vascular leakage in male Wistar rats during and after cardiopulmonary bypass, without altering the endogenous angiopoietin/Tie2 system[1]. Vasculotide (10 μg/kg; intraperitoneal injection; administered 24 h and 1.5 h prior to irradiation, followed by once every other day for 28 consecutive days) TFA reduces acute cutaneous radiation injury in mice, as evidenced by a 43% reduction in the total area of severe desquamation wounds, alleviated inflammatory responses, and improved wound healing[2]. Vasculotide (10 μg/kg; i.p.; pre-irradiation only, continuous administration, post-irradiation only; total 26 days) TFA reduces acute cutaneous radiation injury in mice exposed to 35 Gy irradiation when administered via all tested regimens (pre-irradiation, continuous administration, post-irradiation) TFA, among which the post-irradiation regimen significantly decreases the overall skin injury score by 28%[2]. Vasculotide (250 ng; intraperitoneal injection; once every 48 hours; for 3 months) TFA reduces the superharmonic threshold pressure for focused ultrasound (FUS)-induced blood-brain barrier (BBB) permeability by 21-29% in TgCRND8 mice and accelerates BBB repair, with an 87% BBB closure rate observed 20 hours after FUS treatment in this Alzheimer's disease model[3]. Adjuvant therapy with Vasculotide (500 ng; intravenous injection; 2 administrations) TFA combined with Ampicillin significantly reduces pulmonary permeability, ventilator-induced lung injury (VILI)-related histological damage and edema formation in mice with mechanically ventilated Streptococcus pneumoniae pneumonia, without affecting immune responses or bacterial loads[4].
In Vitro, Vasculotide (28 ng/mL; 3 h) TFA enhances the clonogenic survival rate of irradiated HMVEChTERT cells, with a significant SER value of 1.17[2]. Vasculotide (28 ng/mL; 3 h) TFA preserves the angiogenic capacity of HMVEChTERTs exposed to 4 Gy irradiation, resulting in the formation of tubules comparable to those of non-irradiated cells[2]. Vasculotide (15 min) TFA stimulates the phosphorylation of Tie2 receptors in HMVEChTERTs and activates the downstream AKT pro-survival pathway[2].
References:
[1]. Dekker NAM, et al. Vasculotide, an angiopoietin-1 mimetic, reduces pulmonary vascular leakage and preserves microcirculatory perfusion during cardiopulmonary bypass in rats. Br J Anaesth. 2018;121(5):1041-1051.
[2]. Korpela E, et al. Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model. BMC Cancer. 2014;14:614. Published 2014 Aug 26.
[3]. Lynch M, et al. Vasculotide restores the blood-brain barrier after focused ultrasound-induced permeability in a mouse model of Alzheimer's disease. Int J Med Sci. 2021;18(2):482-493. Published 2021 Jan 1.
[4]. Lask A, et al. Adjunctive therapy with the Tie2 agonist Vasculotide reduces pulmonary permeability in Streptococcus pneumoniae infected and mechanically ventilated mice. Sci Rep. 2022;12(1):15531. Published 2022 Sep 15.