Jung Huang, Ph.D. » Investigators

Cardiovascular Research Interests:

Primary area of research:

• Molecular Mechanism of Atherosclerotic Cardiovascular Disease (ASCVD)
• Prevention and Treatment of ASCVD

Related areas of research:

• TGF-β enhancers and antagonists in the prevention and management of human diseases, including neurodegenerative diseases, cancer, wound healing (e.g., acute and chronic wounds), and tissue fibrosis (keloids, pulmonary fibrosis, and liver cirrhosis)

Summary of cardiovascular research:

For the last several decades, cholesterol has been thought to cause ASCVD. Limiting dietary cholesterol intake has been recommended to reduce the risk of the disease. However, several recent epidemiological studies do not support a relationship between dietary cholesterol and/or blood cholesterol and ASCVD. The role of cholesterol in ASCVD is now uncertain.

Accumulating evidence indicates that TGF-β, an anti-inflammatory cytokine in the circulation, protects against ASCVD and that suppression of canonical TGF-β signaling (Smad2-dependent) is involved in the development of ASCVD. Recently, we demonstrated that 7-dehydrocholesterol (7-DHC; an immediate biosynthetic precursor of cholesterol), but not cholesterol, suppresses canonical TGF-β signaling in target cells/tissues and causes ASCVD in vivo. We have identified TGF-β enhancers that are therapeutic agents for ASCVD in human patients and animal models. They counteract the 7-DHC-mediated suppression of TGF-β canonical signaling in aortic endothelium.

TGF-β enhancers can be classified into 4 types: (i) Type I TGF-β enhancers: cholesterol biosynthesis inhibitors (e.g., statins). (ii) Type II TGF-β enhancers: 7-DHC-extruding compounds, including triterpenoids (e.g., betulinic acid), polyphenols (e.g., cyanidin), antioxidants (e.g., vitamin E), and ethanol. (iii) Type III TGF-β enhancers: endocytosis inhibitors (e.g., dynasore). These agents enhance TGF-β signaling by sustaining TGF-β receptor signaling at the plasma membrane. And (iv) Type IV TGF-β enhancers: fusogenic compounds such as DMSO, ethanol, and resveratrol.  Since, these four types of TGF-β enhancers utilize different mechanisms to enhance such signaling, combinations of these types of TGF-β enhancers with additive and/or synergistic effects may lead to strategies to treat and/or prevent ASCVD and other diseases.