Vascular Endothelial Growth Factor Inhibitors, Salt, and Macrophages: A Complicated Interaction
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See related article, pp 919–926
Cardio-oncology (the cardiovascular care of patients with cancer) has emerged as a new medical discipline, mostly because of targeted cancer therapies, which are effective in cancer treatment but which can cause cardiovascular complications.1 Cardiovascular sequalae of these targeted therapies, which interfere with specific intracellular signaling pathways, may also provide insights into human cardiovascular biology.2 As an example, cardiovascular complications that arise after treatment with vascular endothelial growth factor (VEGF) inhibitors have provided a growing appreciation of VEGF signaling in cardiovascular homeostasis and cardiovascular disease.2
VEGFA, secreted by tumors, plays a critical role in angiogenesis through binding VEGF receptors and activating VEGF signaling pathway (VSP).3 Targeting this pathway (via VEGF inhibitors, also known as VSP inhibitors) has become an important means to treat various cancer types, with 12 such therapies having been approved over the past decade. Most of these therapies are small molecular multitargeted tyrosine kinase inhibitors with sunitinib being the first drug approved. The tyrosine kinase inhibitors in this class can target multiple tyrosine kinase receptors although each is potent against the 3 VEGF receptors: VEGFR1, VEGFR2, and VEGFR3.1 VSP inhibitors also cause many cardiovascular complications, including cardiomyopathy, vascular events, and hypertension. Of these, hypertension is the most common.4 An absolute blood pressure increase is observed 1 week after initiating VSP inhibitors with both systolic and diastolic blood pressure affected. The frequency of hypertension has prompted algorithms by clinicians to recognize and treat the hypertension; however, an intriguing question …