What question did this study set out to answer?

The aim of this study is to evaluate the effects of MnTBAP on right heart failure caused by pulmonary arterial hypertension.

March 24, 2026Open Access

MnTBAP attenuates pulmonary hypertension-induced right ventricular dysfunction and remodeling by modulating the CaMKIIδ-SERCA2a signaling pathway

Key Result

MnTBAP improves right ventricular dysfunction and reverses hypertrophy and fibrosis in pulmonary arterial hypertension models by modulating the CaMKIIδ-SERCA2a signaling pathway.

Key Points

The aim of this study is to evaluate the effects of MnTBAP on right heart failure caused by pulmonary arterial hypertension.
Utilized monocrotaline-induced pulmonary arterial hypertension rat model.
Administered MnTBAP to evaluate its therapeutic effects on right ventricular remodeling.
Measured parameters of right ventricular hypertrophy, fibrosis, and oxidative stress.
MnTBAP inhibited progression of pulmonary arterial hypertension.
Prevented and reversed right ventricular hypertrophy and fibrosis.
Improved right ventricular dysfunction through modulation of CaMKIIδ and SERCA2a signaling.

Structured PICO

Does MnTBAP improve right ventricular dysfunction and remodeling in rats with monocrotaline-induced pulmonary arterial hypertension?

Population

Rats with monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH)

Intervention

Manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP)

Outcome

Right ventricular dysfunction and remodeling (hypertrophy, fibrosis, and oxidative stress)surrogate

In a rat model of PAH, the SOD mimetic MnTBAP attenuates right ventricular remodeling and dysfunction by modulating the CaMKIIδ-SERCA2a signaling pathway.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

A life-threatening condition, pulmonary arterial hypertension (PAH) is typified by the progressive pathological remodeling of pulmonary blood vessels, which progresses to right heart failure (RHF). The pathophysiological mechanisms underlying the progression from PAH to RHF remain unclear. Manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) is a synthetic manganese-based superoxide dismutase (SOD) mimetic with anti-inflammatory and antioxidant properties, attenuating PAH. This study investigated whether MnTBAP directly affects RHF in rats with monocrotaline (MCT)-induced PAH. Our data demonstrated that MnTBAP exerts pleiotropic beneficial effects in MCT-induced PAH rats: it inhibits the progression of PAH, prevents and reverses PAH-mediated right ventricular (RV) hypertrophy, fibrosis, and oxidative stress, and ultimately improves RV dysfunction. Its therapeutic effects are potentially achieved through suppressing aberrant CaMKIIδ phosphorylation in the myocardium of rats with PAH. Meanwhile, MnTBAP was found to downregulate abnormally activated calcineurin A and sodium-calcium exchanger type 1 (NCX1), while restoring the phosphorylation level of phospholamban (PLN), thereby reconstructing the expression of sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) and effectively alleviating MCT‑induced RHF. In conclusion, MnTBAP may exhibit potential therapeutic efficacy in treating PAH‑associated RHF, providing a scientific basis for further research into promising drug candidates for this condition.