A Singapore team of scientists and clinicians from Nanyang Technological University, Singapore (NTU Singapore) and Tan Tock Seng Hospital (TTSH), have developed a three-dimensional (3D) model of the human artery blood vessel wall.
Called an “arterial wall-on-a-chip”, it will help researchers study atherosclerosis, a condition in which cholesterol and inflammatory cells form a plaque on blood vessel walls that results in the vessels narrowing and constricting blood flow, leading to cardiovascular diseases.
Cardiovascular diseases account for some 32 per cent of the deaths worldwide, claiming some 17.9 million lives annually. In Singapore, about 6,990 deaths or about 1/3 of all deaths in 2020 were due to heart disease or stroke.
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This 3D model resembles a sandwich. It comprises a 3D culture of vascular smooth muscle cells, a soft gel layer in the middle, and a layer of endothelial cells that line the inside of the heart and blood vessels. This last layer controls the exchange of molecules between the bloodstream and the surrounding tissues.
The team used this new microfluidic chip, which mimics the cross-section of an arterial wall, to study the effects of oxidative stress on blood vessels, which is usually caused by conditions such as high cholesterol (hyperlipidemia) and inflammation.
Oxidative stress occurs in the human body when there is an imbalance of free radicals and antioxidants. Free radicals are produced during the body’s natural metabolic processes, while antioxidants protect cells and tissues by neutralising these free radicals.
The study, published in the journal Lab on a Chip in June, found that as oxidative stress increase, smooth muscle cells which are found in the middle layer of arteries move inwards, causing inflammation on the endothelial layer on the interior of the artery (See Figure 1 - Structure of an Artery Wall).
There was also more build-up of "bad cholesterol" or low-density lipoprotein (LDL) cholesterol, and immune cells (white blood cells) on the endothelial layer, which contribute towards blood vessel hardening and plaque growth during atherosclerosis.
This was the first time the above effects have been observed in 3D, since previous studies on atherosclerosis have been carried out using animal models, or two-dimensional (2D) cell cultures, which do not fully reveal the interactions between smooth muscle cells and the endothelial layer.
The discovery was made by an interdisciplinary team jointly led by Assistant Professor Hou Han Wei from the NTU School of Mechanical and Aerospace Engineering, and Senior Consultant, Endocrinology, TTSH, Associate Professor Rinkoo Dalan, who is a joint faculty with the Lee Kong Chian School of Medicine, in collaboration with Assistant Professor Dalton Tay from the NTU School of Materials Science and Engineering.