Arginase Inhibition Mitigates Bortezomib-Exacerbated Cardiotoxicity in Multiple Myeloma

Area of Science:

• Cardiovascular research
• Oncology
• Pharmacology

Background:

• Multiple myeloma (MM) increases cardiovascular risk, and its therapies can cause cardiac damage.
• Impaired nitric oxide (NO) pathways and endothelial dysfunction are potential mechanisms for this cardiotoxicity.

Purpose of the Study:

• To investigate if an arginase inhibitor can mitigate cardiotoxicity induced by MM and bortezomib.
• To assess the role of endothelial function and NO pathways in MM- and bortezomib-induced cardiotoxicity.

Main Methods:

• Utilized a Vĸ*MYC mouse model of non-light chain multiple myeloma.
• Assessed cardiac function using echocardiography and measured NO production.

Main Results:

• MM caused progressive left ventricular systolic dysfunction, exacerbated by bortezomib.
• The arginase inhibitor OAT-1746 offered partial protection against MM and bortezomib cardiotoxicity.
• Endothelial function and NO levels were not the primary mediators of these cardiac effects.

Conclusions:

• Bortezomib worsens MM-related cardiac dysfunction; arginase inhibitors provide partial protection.
• Endothelial function does not appear to mediate these adverse or beneficial effects.
• Arginase inhibitors may hold promise for preventing or treating cardiotoxicity in multiple myeloma patients.