A CUHK pathfinder purifies patients’ hearts

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Prof Huang Yu (right) and Dr Wang Li conduct a study that sets new treatment directions to cardiovascular diseases.

Hong Kong – What is the common cause of heart attacks, strokes and kidney failure? The answer lies in our blood vessels. The dysfunction in the endothelial cells that line the inside of blood vessels triggers a cascade of events in the body, ultimately leading to hardening of the arteries and the formation of blood clots.

Spending more than a decade tracing the culprit, Prof Huang Yu at the School of Biomedical Sciences at the Chinese University of Hong Kong (CUHK) has identified the chemical pathways that cause those endothelial cells to malfunction.

The endothelial cells emit an anti-inflammatory gas molecule, nitric oxide, whose production is essential in regulating damage to the cardiovascular system. The chemical curbs the contraction, growth, aggregation and inflammation of surrounding smooth-muscle cells, avoiding vascular damage.

Professor Huang and his postdoctoral fellow Wang Li discovered and proved that the Hippo signaling pathway, which tells endothelial cells how to react, responds differently to varied patterns of blood flow. A straight blood vessel with normal blood flow can stimulate the endothelial cells to produce nitric oxide. On the contrary, if blood vessels are curved or arched, or have narrow branches, the flow gets disturbed. This would increase production of the free radicals that induce inflammation, as well as reducing the production of beneficial nitric oxide.

“Nitric oxide controls the ‘bad guys’ when you’re healthy,” Professor Huang says. “Then when, for whatever reason, you produce too many free radicals in your blood vessels, nitric oxide starts to lose its capacity to protect blood vessels.” Despite its importance, nitric oxide could exist for seconds only.

Uncovering how the Hippo pathway signals to other cells will allow for the screening of existing small-molecule drugs to see if they are effective in targeting the pathway in the treatment of atherosclerosis, a disease in which plaque builds up in arteries, hardening and narrowing them over time. The results can serve as a ground for repurposing existing drugs to reverse the harmful effect of blood vessel dysfunctions. In fact, Professor Huang’s team have recently discovered that drugs designed to prevent high blood pressure and also diabetes have the additional effect of preserving the production of nitric oxide in endothelial cells.

While it was proved that exercise could help endothelial cells to function normally, there are a number of ways to stimulate the production of nitric oxide, e.g. vitamin D, polyphenols from green or black tea, red wine and several Chinese herbs. Professor Huang has already started studying why polyphenols stimulate the production of nitric oxide. People with high blood pressure, diabetes and obesity normally do not have proper function of nitric oxide. Prolonging and stimulating the existence of nitric oxide thus improves one’s health.

Professor Huang’s study was recognised, and brought him a research fund sponsored by the government which supports another study of his which investigates how physical exercise helps with vascular health. It was the first study of the topic ever conducted in Hong Kong. Professor Huang is working closely with clinicians to see if the knowledge can be put to use in patients with diabetes, hypertension or atherosclerosis. Ultimately, he hopes the theory will lead to very profound practice.