Cardiac amyloidosis is a secondary phenomenon of an already pre-existing chronic condition. Whether cardiac amyloidosis represents one of the complications post myocardial infarction (MI) has yet to be fully understood. Here, we show that amyloidosis occurs after MI and that amyloid fibers are composed of macrophage-derived serum amyloid A 3 (SAA3) monomers. SAA3 overproduction in macrophages is triggered by exosomal communication from cardiac stromal cells (CSCs), which, in response to MI, activate the expression of a platelet aggregation-inducing type I transmembrane glycoprotein, Podoplanin (PDPN). CSC