Circulating mediators of remote ischemic preconditioning: search for the missing link between non-lethal ischemia and cardioprotection Circulating mediators of remote ischemic preconditioning: search for the missing link between non-lethal ischemia and cardioprotection

Autophagy is a cellular process by which mammalian cells degrade and assist in recycling damaged organelles and proteins. This study aimed to ascertain the role of autophagy in remote ischemic preconditioning (RIPC)-induced cardioprotection. Sprague Dawley rats were subjected to RIPC at the hindlimb followed by a 30-min transient blockade of the left coronary artery to simulate ischemia reperfusion (I/R) injury. Hindlimb muscle and the heart were excised 24 h post reperfusion. RIPC prior to I/R upregulated autophagy in the rat heart at 24 h post reperfusion. In vitro, autophagy inhibition or stimulation prior to RIPC, respectively, either ameliorated or stimulated the cardioprotective effect, measured as improved cell viability to mimic the preconditioning effect. Recombinant interleukin-6 (IL-6) treatment prior to I/R increased in vitro autophagy in a dose-dependent manner, activating the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway without affecting the other kinase pathways, such as p38 mitogen-activated protein kinases (MAPK), and glycogen synthase kinase 3 Beta (GSK-3β) pathways. Prior to I/R, in vitro inhibition of the JAK-STAT pathway reduced autophagy upregulation despite recombinant IL-6 pre-treatment. Autophagy is an essential component of RIPC-induced cardioprotection that may upregulate autophagy through an IL-6/JAK-STAT-dependent mechanism, thus identifying a potentially new therapeutic option for the treatment of ischemic heart disease.

Cardiovascular diseases including myocardial infarctions, myocarditis, strokes, coronary artery disease, chronic granulomatous disease, atherosclerotic cardiovascular disease, etc. can be regarded as the severe health trouble round the globe. The reasons behind the heart related complications have been well chalked our so far. Interestingly, along with the non-infectious reasons, an array of bacteria, fungi, parasites and viruses is known to cause different types of heart complications. Unfortunately, the role of microorganisms in inducing heart diseases is not that much known by the mass community in the underdeveloped and even in the developing countries over the world. However, among the microorganisms causing heart diseases, the multifaceted bionetwork by the gut microorganisms especially drew the interests of microbiologists. The impairment of cardiac membrane, the metabolic malfunction of heart, and imbalance in the functionality of the immune cells by the alternation in the composition of gut microorganisms are currently not unknown. Present review outlined the onset of heart diseases caused by the gut microflora in a simple way which would be important in public health regard.