Red blood cell-derived semaphorin 7A promotes thrombo-inflammation in myocardial ischemia-reperfusion injury through platelet GPIb

Abstract

Myocardial ischemia is one of the leading health problems worldwide. Therapy consists of the restitution of coronary perfusion which is followed by myocardial inflammation. Platelet-neutrophil interaction is a crucial process during inflammation, yet its consequences are not fully understood. Here, we show that platelet-neutrophil complexes (PNCs) are increased in patients with acute myocardial infarction and that this is associated with increased levels of neuronal guidance protein semaphorin 7A (SEMA7A). To investigate this further, we injected WT animals with Sema7a and found increased infarct size with increased numbers of PNCs. Experiments in genetically modified animals identify Sema7a on red blood cells to be crucial for this condition. Further studies revealed that Sema7a interacts with the platelet receptor glycoprotein Ib (GPIb). Treatment with anti-Sema7a antibody protected from myocardial tissue injury. In summary, we show that Sema7a binds to platelet GPIb and enhances platelet thrombo-inflammatory activity, aggravating post-ischemic myocardial tissue injury.

Piperine protects against pyroptosis in myocardial ischaemia/reperfusion injury by regulating the miR‐383/RP105/AKT signalling pathway

“…Timely and effectively reperfusion acts as most efficacious remedy for AMI 4,6 . However, accompanying MIRI largely offset this beneficial effect 4,6 .…”

“…Echo assay was used to determine left ventricular (LV) function as previously demonstrated 3,4,6 . The transthoracic echocardiograms were recorded using a MyLab 30CV ultrasound system (Biosound Esaote, Inc.).…”

“…Currently, the most effective way to save dying cardiomyocytes induced by acute myocardial infarction (AMI) is timely revascularization 1‐5 . However, re‐establishing blood to ischaemic area yields additional myocardial damages known as myocardial ischaemia/reperfusion (I/R) injury (MIRI) 1‐3 .…”

Roles of TRAFs in Ischemia-Reperfusion Injury

“…Myocardial infarction remains one of the leading health problems around the world. However, recanalization of previously blocked blood vessels can cause serious myocardial IRI, which is a leading risk factor for heart failure (Zhu et al, 2019;Kohler et al, 2020). An early myocardial reperfusion period can cause endoplasmic reticulum (ER) stress and subsequently increase the expression of ER stress markers, including TRAF2 (Wang Z. H. et al, 2014).…”

“…IRI can occur in a variety of tissues and organs, including the liver, kidney, heart, lung, brain, intestine, and retina, leading to severe pathophysiological damage to the primary organ or even remote organs, partly due to explosive oxidative stress, inflammation and destruction of the physiological body barrier. The occurrence of IRI leads to a poor prognosis in many diseases, such as neuronal damage caused by ischemic shock, acute cardiopulmonary damage caused by thrombolytic therapy, and visual impairment caused by retinopathy (Chen et al, 2017;Li et al, 2019d;Hui et al, 2020;Kohler et al, 2020). However, there is still no exact treatment method in clinical guidelines due to the devastating pathological damage and complex molecular mechanisms involved in IRI.…”