Gamma-Oryzanol Attenuates Aortic Valve Interstitial Cell Calcification via Suppression of BMP2-SMAD and MAPK...

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Pharmacology

Background:

• Calcific aortic valve stenosis (CAVS) is a progressive disease driven by oxidative stress and the osteogenic differentiation of valvular interstitial cells (VICs).
• Currently, no pharmacological treatments exist to halt the progression of CAVS.
• Gamma-oryzanol (γ-ORZ), a natural compound from rice bran, possesses significant antioxidative and anti-inflammatory properties.

Purpose of the Study:

• To investigate the potential of γ-ORZ in mitigating oxidative stress and preventing osteogenic differentiation in valvular interstitial cells (VICs).
• To explore the underlying molecular mechanisms by which γ-ORZ may counteract valvular calcification.

Main Methods:

• Porcine VICs (pVICs) were treated with PCM to induce oxidative stress and calcification.
• γ-ORZ was administered to assess its effects on intracellular ROS, osteogenic markers, and calcium deposition.
• RT-qPCR and Western blot analyses were employed to evaluate gene and protein expression related to calcification and signaling pathways.

Main Results:

• γ-ORZ significantly reduced PCM-induced ROS elevation, osteogenic differentiation, and calcium phosphate deposition in pVICs.
• Treatment with γ-ORZ led to the downregulation of key calcification markers, including RUNX2, OPN, and BMP2.
• γ-ORZ suppressed SMAD1/5/9 transcription and phosphorylation, decreased p38/ERK MAPK activation, and reduced ALP activity.

Conclusions:

• γ-ORZ effectively mitigates oxidative stress-mediated valvular calcification in VICs.
• The compound acts by inhibiting both canonical and non-canonical BMP2-SMAD and MAPK signaling pathways.
• γ-ORZ demonstrates potential as a therapeutic candidate for early intervention in calcific aortic valve stenosis (CAVS).