Phosphorylcholine Antibodies Preserve Cardiac Function and Reduce Infarct Size by Attenuating the Post-Ischemic Inflammatory Response

Identification of IgG1 isotype phosphorylcholine antibodies for the treatment of inflammatory cardiovascular diseases

“…PC‐mAb preserves coronary flow reserve and attenuates atherosclerotic inflammation as determined by the uptake of 18F‐fluorodeoxyglucose in atherosclerotic LDLR −/− ApoB 100/100 mice [ 45 ]. Furthermore, PC‐mAb showed preserved cardiac function and reduced infarct size in hypercholesterolaemic mice [ 46 ]. ATH3G10 did not cause adverse reactions in toxicity studies opening up the step towards clinical studies.…”

Phosphorylcholine antibodies restrict infarct size and left ventricular remodelling by attenuating the unreperfused post‐ischaemic inflammatory response

“…These results suggest PC‐mAb treatment to be a potential therapeutic agent against ischaemic‐induced heart failure in the absence of reperfusion. Previously, we demonstrated PC‐mAb treatment to additionally preserve cardiac function following myocardial ischaemia‐reperfusion injury, 41 suggesting a point of no return regarding preservation of cardiac function in the absence of reperfusion, endorsing the relevance and impact of selecting different models of myocardial ischaemia 50 …”

“…PC‐mAb blocks oxLDL uptake by macrophages and inhibits vascular remodelling in a mouse model for accelerated atherosclerosis and preserves coronary flow reserve and attenuates atherosclerotic inflammation 40 . Above all, it attenuates the immediate inflammatory response following myocardial ischaemia‐reperfusion injury in hypercholesterolaemic APOE*3‐Leiden mice, preserving cardiac function with an increased ejection fraction of 33% 41 . As unreperfused transmural MI yet remains a significant determinant in worldwide morbidity and mortality, pressing heavily on the healthcare system and costs, additional therapeutic effects of PC‐mAb following unreperfused MI might be of interest.…”

“… 40 Above all, it attenuates the immediate inflammatory response following myocardial ischaemia‐reperfusion injury in hypercholesterolaemic APOE*3‐Leiden mice, preserving cardiac function with an increased ejection fraction of 33%. 41 As unreperfused transmural MI yet remains a significant determinant in worldwide morbidity and mortality, pressing heavily on the healthcare system and costs, additional therapeutic effects of PC‐mAb following unreperfused MI might be of interest. Furthermore, hypercholesterolaemia causes a pro‐inflammatory phenotype characterized by monocytosis, 42 , 43 making it an important factor to consider in experimental studies.…”

Post-ischemic Myocardial Inflammatory Response: A Complex and Dynamic Process Susceptible to Immunomodulatory Therapies

“…Attenuating the pro-inflammatory phase by targeting Ly-6C hi monocytes or M1 macrophages has been shown cardioprotective following reduction of interferon regulatory factor 5 (IRF5) expression ( 198 ), injection of phosphatidylserine (PS)-presenting liposomes ( 199 ), or irbesartan-nanoparticles ( 200 ), as well as administration of annexin A5 (AnxA5) ( 201 ) or phosphorylcholine monoclonal immunoglobulin G antibodies ( 202 ), and CCR-2 silencing ( 203 ). In addition, expediting the differentiation from reparative Ly-6C lo monocytes toward M2 macrophages by administration of pioglitazone-nanoparticles ( 204 ) or topiramate ( 205 ), T reg -cell activation ( 206 ), and silencing the collapsin response mediator protein-2 (CRMP2) ( 207 ) limited adverse remodeling.…”