Cancer drives atherosclerotic plaque vulnerability by inducing pathological angiogenesis

Area of Science:

• Oncology
• Cardiology
• Immunology

Background:

• Cardiovascular disease (CVD) is a leading cause of death in cancer survivors.
• Traditionally, CVD in survivors is attributed to shared risk factors and chemotherapy side effects.
• This study investigates the direct role of cancer in promoting atherosclerosis.

Purpose of the Study:

• To determine if cancer directly promotes atherosclerosis.
• To elucidate the mechanisms by which cancer accelerates cardiovascular events.
• To identify potential therapeutic targets for preventing CVD in cancer patients.

Main Methods:

• Propensity-matched analyses of cardiovascular event rates in cancer patients.
• Atheroprone mouse models implanted with colorectal tumors.
• Assessment of plaque vulnerability, pathological angiogenesis, and intraplaque hemorrhage.
• Analysis of tumor-secreted TNF-α and its induction of LRG1.

Main Results:

• Cancer patients exhibited significantly elevated cardiovascular event rates, independent of comorbidities.
• Tumor-bearing mice showed accelerated atherosclerosis with increased plaque vulnerability and intraplaque hemorrhage.
• Tumor-secreted TNF-α induced LRG1, a pro-angiogenic factor, in murine models and human plaques.
• Therapeutic interventions (cytokine inhibitors, tumor resection) prevented plaque destabilization in mice.

Conclusions:

• Cancer causally promotes atherosclerosis and cardiovascular disease.
• Tumor-derived TNF-α and induced LRG1 are key mediators of this process.
• Targeting these pathways offers novel translational strategies for reducing CVD in cancer survivors.