Nitric Oxide Synthase 2 Induction Promotes Right Ventricular Fibrosis

Area of Science:

• Cardiovascular Biology
• Pulmonary Hypertension Pathophysiology
• Molecular Medicine

Background:

• Right ventricular (RV) function is critical for survival in pulmonary arterial hypertension (PAH).
• Nitric oxide (NO) can reduce RV afterload but excessive amounts cause oxidative stress, driving RV remodeling.
• Oxidative stress exacerbates pulmonary arteries and RV remodeling in PAH.

Purpose of the Study:

• To investigate the role of nitric oxide synthase 2 (NOS2) induction in RV adaptation to pressure overload.
• To determine if NOS2-driven NO production contributes to oxidative stress and RV remodeling in PAH.

Main Methods:

• A surgical pulmonary artery banding (PAB) mouse model was used to induce RV dysfunction.
• NOS2 expression, NO production, and reactive oxidant formation were assessed in RV tissue.
• RV remodeling, collagen deposition, and cardiac function were evaluated in wild-type and NOS2-deficient mice.

Main Results:

• PAB increased NOS2 expression, NO production, and reactive oxidants in the RV.
• NOS2 deficiency reduced oxidative stress and collagen accumulation in the RV after PAB.
• No significant differences in RV function were observed between genotypes post-PAB.

Conclusions:

• NOS2 induction plays a profibrotic role in the hypertrophied RV during PAH.
• Targeting NOS2 may offer a therapeutic strategy to reduce RV fibrosis and improve adaptation to PAH.