Beyond the Bite: Tick Salivary Proteins Targeting Hemostasis and Inflammation; Implications for Cardiovascular Disease.

Ticks have evolved a diverse repertoire of salivary proteins that enable prolonged blood feeding by finely modulating host hemostatic, vascular, and immune responses, providing an unexpected source of candidates for cardiovascular and anti-inflammatory therapy. Tick saliva contains molecules that interfere with vasoconstriction, platelet activation, coagulation and fibrinolysis, while at the same time shaping leukocyte recruitment and cytokine release, placing these proteins at the crossroads of hemostasis, inflammation and cardiovascular disease. In this review, the main families of tick-derived effectors are discussed, including thrombin and factor Xa inhibitors, apyrases, serpins, and multispecific proteins that act on both coagulation and inflammatory pathways, with an emphasis on how their mechanisms could be harnessed for anti-thrombotic and anti-inflammatory therapies. Particular attention is given to salp proteins and the chemokine-binding evasins, which remodel chemokine networks and immune cell trafficking in models of atherosclerosis, ischemia-reperfusion injury and stroke, where they can dampen leukocyte infiltration, matrix degradation and plaque destabilization. Taken together, these insights show how millions of years of tick-host coevolution have produced a molecular toolkit that not only clarifies fundamental aspects of thromboinflammation, but also provides a basis for next-generation biologics targeting cardiovascular and inflammatory disorders.