Decreased intracellular chloride promotes ADP induced platelet activation through inhibition of cAMP/PKA instead of activation of Lyn/PI3K/Akt pathway.

Decrease of chloride concentration contributes to cardiovascular diseases, however, whether decrease of chloride concentration is involved in platelet activation remains elusive. In the present study, we found that ACI patients had lower serum chloride which would be rescued after Aspirin administration. ADP induced chloride concentration reduction in platelets. Blockade of chloride channel prevented ADP-induced platelet adhesion, activation and aggregation, however, decreasing the extracellular chloride concentration promoted ADP-induced platelet adhesion and activation. Decrease of the extracellular chloride concentration facilitated the inactivation of Src family kinase Lyn, which was not involved in PI3K/Akt phosphorylation. Nevertheless, low chloride concentration promoted the production of platelet cytosol Gαi2 subunit. This subunit prevents AC from converting ATP into cAMP, which therefore, inhibited the phosphorylation of PKA to promote platelet activation. In conclusion, decreased intracellular chloride promotes ADP induced platelet activation through the Gαi2/cAMP/PKA pathway instead of the Lyn/PI3K/Akt signal pathway.

Subtalar joint pigmented villonodular synovitis misdiagnosed at the first visit: A case report.

BACKGROUND: Pigmented villonodular synovitis (PVNS) is an uncommon disease that usually occurs in large joints, and involvement of the subtalar joint is rare. The lack of comprehensive knowledge of subtalar joint PVNS could lead to misdiagnosis. CASE SUMMARY: We present a 64-year-old woman who, at her first visit, complained of discomfort in the right ankle when she walked. Based on the physical signs and X-ray report, the physician failed to make the suspected diagnosis of PVNS. Eighteen months later, the patient returned with a complaint of a mass in her right lateral malleolus with intermittent blunt pain. The X-ray presented an osteophyte formation and soft tissue calcification at the margin of the subtalar joint. The laboratory tests were normal, whereas magnetic resonance imaging (MRI) showed a low-intensity area on both T1- and T2-weighted images. A suspected diagnosis of PVNS was made and later confirmed by postoperative pathology. Subsequently, the patient received radiotherapy with 32 Gy in 16 fractions. At 6 mo postoperatively, the patient only complained of discomfort after walking three blocks. The American Orthopedic Foot and Ankle Society Ankle-Hindfoot score was 97. CONCLUSION: MRI is necessary for the diagnosis of PVNS. Early soft tissue calcification and painless joint swelling should be of concern.