miR-195-3p/BDNF axis regulates hypoxic injury by targeting P-ERK1/2 expression

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Cellular Physiology

Background:

• Coronary heart disease (CHD) is a leading cause of global mortality.
• Endothelial cell (EC) dysfunction, including apoptosis and inflammation, is central to CHD pathogenesis.
• Understanding the molecular mechanisms underlying EC response to hypoxia is crucial for developing new therapies.

Purpose of the Study:

• To investigate the expression and function of microRNA-195-3p and brain-derived neurotrophic factor (BDNF) in human umbilical vein endothelial cells (HUVECs) under hypoxic conditions.
• To elucidate the role of the microRNA-195-3p/BDNF signaling pathway in regulating EC apoptosis and survival.
• To explore the potential of targeting this axis as a therapeutic strategy for CHD.

Main Methods:

• Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia using the anaerobic tank method.
• Quantitative analysis of microRNA-195-3p and BDNF expression levels.
• Assessment of apoptosis markers and mitochondrial pathway proteins (Bcl-2/BAX).
• Pharmacological inhibition of microRNA-195-3p to evaluate its effects on cellular responses.

Main Results:

• Hypoxia led to increased expression of microRNA-195-3p and BDNF, accompanied by elevated EC apoptosis.
• The BDNF/P-ERK1/2 pathway was found to regulate the mitochondrial apoptosis pathway (Bcl-2/BAX), which was downregulated.
• Inhibition of microRNA-195-3p reversed these effects, downregulating BDNF and P-ERK1/2, upregulating Bcl-2/BAX, and partially mitigating hypoxic injury.

Conclusions:

• The microRNA-195-3p/BDNF/P-ERK1/2/Bcl-2/BAX axis plays a significant role in EC function under hypoxia.
• Targeting this axis offers a potential therapeutic avenue to preserve EC function and improve outcomes in CHD.
• This pathway represents a novel treatment strategy for managing hypoxic-induced endothelial dysfunction in cardiovascular diseases.