Low molecular weight heparin treatment reduced apoptosis and oxidative cytotoxicity in the thrombocytes of patients with recurrent pregnancy loss and thrombophilia: Involvements of TRPM2 and TRPV1 channels

• Published in: The journal of obstetrics and gynaecology research 2023-05, Vol.49 (5), p.1355-1365
• Main Authors: Dal, Yusuf, Nazıroğlu, Mustafa, Özkaya, Mehmet Okan
• Format: Article
• Language: English
• Subjects: Animals; Anthranilic acid; Apoptosis; Blood Platelets - metabolism; Calcium (intracellular); Calcium - metabolism; Calcium - pharmacology; calcium signaling; Calcium signalling; Capsaicin receptors; Capsazepine; Caspase; Cell death; Cytotoxicity; Heparin; Heparin, Low-Molecular-Weight - pharmacology; Humans; low molecular weight heparin; Membrane potential; Mitochondria; Molecular weight; oxidative cytotoxicity; Oxidative Stress; Platelets; Pregnancy; Rats; Rats, Wistar; Reactive oxygen species; Reactive Oxygen Species - metabolism; recurrent pregnancy loss; thrombocytes; Thrombophilia; Transient receptor potential proteins; TRPM Cation Channels - metabolism; TRPV Cation Channels - metabolism; TRPV Cation Channels - pharmacology
• ISSN: 1341-8076; 1447-0756
• DOI: 10.1111/jog.15612

Aim Recurrent pregnancy loss (RPL) is known to be associated with increased thrombophilia and oxidative toxicity. However, the mechanism of thrombophilia apoptosis and oxidative toxicity is still unclear. In addition, the treatment of heparin induced regulator roles on intracellular free Ca2+ ([Ca2+]i) and cytosolic reactive oxygen species (cytROS) concentrations in several diseases. TRPM2 and TRPV1 channels are activated by different stimuli, including oxidative toxicity. The aim of this study was to investigate the effects of low molecular weight heparin (LMWH) via modulation of TRPM2 and TRPV1 on calcium signaling, oxidative toxicity, and apoptosis in the thrombocytes of RPL patients. Study Design Thrombocyte and plasma samples collected from 10 patients with RPL and 10 healthy controls were used in the current study. Main Findings The [Ca2+]i concentration, cytROS (DCFH‐DA), mitochondrial membrane potential (JC‐1), apoptosis, caspase‐3, and caspase‐9 levels were high in the plasma and thrombocytes of RPL patients, although they were diminished by the treatments of LMWH, TRPM2 (N‐(p‐amylcinnamoyl)anthranilic acid) and TRPV1 (capsazepine) channel blockers. Conclusions The current study results suggest that the treatment of LMWH is useful against apoptotic cell death and oxidative toxicity in the thrombocytes of patients with RPL, which seem to be dependent on increased levels of [Ca2+]i concentration via the activation of TRPM2 and TRPV1.