Atherothrombotic events such as myocardial infarction and ischemic stroke are a major cause of morbidity and mortality worldwide. Understanding the molecular and cellular mechanisms of... Show moreAtherothrombotic events such as myocardial infarction and ischemic stroke are a major cause of morbidity and mortality worldwide. Understanding the molecular and cellular mechanisms of atherosclerotic plaque destabilization or erosion, and developing new therapeutics to prevent acute cardiovascular events is important for vascular biology research and clinical cardiovascular medicine. However, basic research on plaque destabilization, rupture and erosion is hampered by the lack of appropriate animal models of atherothrombosis. Unprovoked atherothrombosis is very scarce in commonly used mouse models for atherosclerosis, the low-density lipoprotein receptor knockout and apolipoprotein E knockout mice. Therefore, specific interventions are required to induce atherothrombosis in these models. Two strategies can be employed to induce atherothrombosis: 1) plaque destabilization and 2) induction of blood hypercoagulability. Although the individual strategies yield atherothrombosis at low incidence, it appears that the combination of both plaque destabilization and an increase in blood coagulability is the most promising strategy to induce atherothrombosis on a larger scale. In this review, we summarize the recent developments on mouse models for the investigation of atherothrombosis. Show less
Ouweneel, A.B.; Heestermans, M.; Verwilligen, R.A.F.; Gijbels, M.J.J.; Reitsma, P.H.; Eck, M. van; Vlijmen, B.J.M. van 2017
Murine atherosclerosis models do not spontaneously develop atherothrombotic complications. We investigated whether disruption of natural anticoagulation allows preexisting atherosclerotic plaques... Show moreMurine atherosclerosis models do not spontaneously develop atherothrombotic complications. We investigated whether disruption of natural anticoagulation allows preexisting atherosclerotic plaques to progress toward an atherothrombotic phenotype. Mice featured clots in the left atrium of the heart. Our findings indicate that small interfering RNA-mediated silencing of protein C in apolipoprotein E-deficient mice creates a condition that allows the occurrence of spontaneous atherothrombosis, albeit at a low incidence. Lowering natural anticoagulation in atherosclerosis models may help to discover factors that increase atherothrombotic complications. Show less
