Anti-thrombotic drugs could be one step further, say researchers – ScienceDaily

The results allow researchers to take another step toward developing new antithrombotic drugs without the serious side effects that cause life-threatening bleeding.

Although coagulation – the activation of platelet coagulation – is essential for stopping blood loss from a cut or wound, overactivation can lead to blood clots, heart attack or stroke.

The researchers used a microfluidic channel, mimicking the narrowing of vessels responsible for blood clots, to observe platelet activation under the physiological conditions of blood clotting.

Posted in the journal Nature Materials, the researchers demonstrated that disruption of blood flow could lead to an intermediate activation of integrin, which was previously unrecognized, the adhesion receptor involved in platelet aggregation to form a clot. Integrin is a mechanosensory protein that platelets use to detect the mechanical force generated by dynamic blood flow.

"Integrins fundamentally facilitate how cells bind to and respond to their mechanical environment," said Arnold Lining Ju, co-lead author of the Heart Research Institute (HRI) of the School of Aerospace Mechanical Engineering. and mechatronics from the University of Sydney. and Charles Perkins Center (CPC).

"They allow the cells to hook to each other and are great communicators, transmitting bidirectional signals to activate the link function, and from the outside to the inside, allowing the cell to detect the extracellular environment and react to it.Intrine can also instruct platelet cells. "coagulation behaviors."

Dr. Ju, a DECRA member of the Australian Council for Biomedical Engineering Research at AMME and HRI, has worked with a team of international researchers to develop a single-molecule biomechanical nanotool called a dual "probe." Biomembrance Strength (BFP) "to observe how platelets capture mechanical strength. in the blood stream to exert adhesive coagulation functions.

The researchers argue that the finding – that biomechanical growth of thrombi is primarily mediated by an intermediate state triggered by a single pathway of biomechanical integrin activation – could guide the development of novel antithrombotic strategies. This could benefit many of the 55,000 Australians who suffer a heart attack each year – one every 10 minutes.

"Our discovery could also help diabetic patients because diabetic platelets are more resistant to conventional anticoagulant drugs," said Dr. Ju. "Targeting biomechanical pathways may also have the advantage of preventing the formation of deadly clots without the side effects of bleeding.

Dr. Ju's research also provides a new explanation for the low effectiveness of conventional antiplatelet drugs in the treatment of thrombotic cardiovascular diseases. Although these drugs inhibit the biochemical activation of platelets, they can not block the biomechanical signaling pathways of platelets.

"Antiplatelet drugs such as aspirin, clopidogrel, and ticagrelor are commonly used for the treatment of thrombotic diseases, but these drugs have serious side effects that cause fatal bleeding," said Dr. Ju.

"For a long time, studies in the field of thrombosis have attempted to understand the mechanism of platelet activation at the cellular and molecular levels, and hoped to provide insights for the development of new high-efficiency antithrombotic drugs with few drugs." 39, side effects. "

Yuping Yuan, Senior Fellow at HRI, said, "Diabetes is the biggest threat to the Australian health care system, and this discovery highlights the protection of vulnerable diabetics from heart disease."

The phenomenon of "mechanically activated platelet activation" found in the study explains why platelets can aggregate and accumulate by mechanical stimulation of turbulence at high velocity only, causing the blockage of a blood vessel.

Therefore, this research provides new insights for the development of innovative and highly effective antithrombotic drugs without serious side effects on bleeding.