A new scientific publication by Li-Ming Lien et al. has been issued in the International Journal of Molecular Sciences, describing new findings about the role of phospholipase D1 (PLD1) and phospholipase D2 (PLD2) in thrombus formation in mice.
PLD activity has been previously described to play a role in thrombotic events in mammals, making it a potential pharmacological target for the prevention of thrombotic diseases. However, the exact roles and functions of the two isoforms PLD1 and PLD2 likely differ between species. Understanding the implications of the isoforms in different species such as mice and humans is of crucial importance in order to properly design and interpret studies. Therefore, Mien et al. studied the effects of selective inhibition of PLD1 and PLD2, respectively, in mice on thrombosis-associated events, i.e. pulmonary thrombosis and middle cerebral artery occlusion (MCAO)-induced brain injury.
The experimental set-up was essentially based on the use of the Microvisioneer manualWSI, allowing to assess the presence of ADP-induced acute pulmonary thrombosis via the detection of occlusive thrombi in pulmonary vessels in HE-stained lung tissue sections. The histological evaluations accompanied by a determination of survival rates showed that selective inhibition of PLD2 did not show any protection against ADP-based induction of lethal pulmonary thrombosis, while the selective inhibition of PLD1 exerted a slight and significant protective effect on survival rates; a combined inhibition of PLD1 and PLD2 led to an even more pronounced protective effect, similar to that observed for aspirin treatment.
Similar outcomes, i.e. a protective effect of PLD1 inhibition and an even greater protection via concurrent inhibition of PLD1 and PLD2, were likewise observed for parameters representative of MCAO-induced brain injury.
Overall, the findings showed that of the two isoforms, PLD1 played a more crucial role in thrombotic events than PLD2 in mice. Further, both enzymes could act synergistically or have partially redundant functions.
Li-Ming Lien, Wan-Jung Lu, Ting-Yu Chen, Tzu-Yin Lee, Hsueh-Hsiao Wang, Hsien-Yu Peng, Ray-Jade Chen, Kuan-Hung Lin: Phospholipase D1 and D2 Synergistically Regulate Thrombus Formation, International Journal of Molecular Sciences, 2020
DOI: 10.3390/ijms21186954 https://doi.org/10.3390/ijms21186954