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bioRxiv · 10.64898/2026.01.18.700232

Cancer drives atherosclerotic plaque vulnerability by inducing pathological angiogenesis

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Abstract

Cardiovascular disease (CVD) is the leading cause of death for many cancer survivors, a phenomenon traditionally attributed to shared risk factors and cardiotoxic chemotherapies. Here, we hypothesized that cancer may also directly promote atherosclerosis. Propensity-matched analyses confirmed significantly elevated cardiovascular event rates amongst cancer patients, independent of comorbidities such as smoking. Atheroprone mice implanted with colorectal tumors demonstrated accelerated features of plaque vulnerability, driven by pathological angiogenesis and intraplaque hemorrhage. Mechanistically, tumor-secreted TNF- induced the pro-angiogenic factor LRG1 across multiple murine models and human plaques. Therapeutic interventions targeting these pathways, including with FDA-approved cytokine inhibitors or tumor resection, prevented plaque destabilization in mice and reduced coronary revascularization rates in patients. Together, these findings suggest that cancer may causally promote CVD and unveil novel translational strategies for cancer survivors.

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Luo, L., Fu, C., Jarr, K.-U., Baylis, R., Sun, V. H., Heemelaar, J., von Scheidt, M., Ramirez, D., Krefting, J., Sachs, N., Wettich, J. L., Winter, H., Gao, H., Wang, F., Adkar, S., Haas, A., Gonzalez, M., Nead, K. T., Maegdefessel, L., Schunkert, H., Neilan, T. G., Leeper, N. J.. 2026-01-20. Cancer drives atherosclerotic plaque vulnerability by inducing pathological angiogenesis. https://doi.org/10.64898/2026.01.18.700232

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