Figure 9: Proposed TS Signal Transduction Cascade

ISO injection results in β-adrenoceptor activation, leading to activation of coupled endothelial nitric oxide synthase (eNOS) receptors and to mitochondrial reactive oxygen species release. With increased superoxide (O2) and nitric oxide (NO) production, there is formation of peroxynitrite (ONOO), leading to protein nitration, myocardial inflammation, and poly(ADP-ribose) polymerase-1 (PARP-1) activation, resulting in energetic impairment as well as PAR production. Inflammatory activation of glycocalyx shedding contributes to the development of edema and to increased expression of TXNIP. ATP = adenosine triphosphate; BNP = B-type natriuretic peptide; DNA = deoxyribonucleic acid; iNOS = inducible nitric oxide synthase; NAD+ = nicotinamide adenine dinucleotide; other abbreviations as in Figure 3.