Figures & data
Figure 1 The generation of reactive oxygen species following inhibition of the neuregulin/HER2 pathway.
Abbreviations: HER, human epidermal growth receptor; ANG II, angiotensin II; NADPH, nicotinamide adenine dinucleotide phosphate-oxidase; PGDF, platelet-derived growth factor; TGF-α, tumor growth factor-alpha.
Figure 2 The effects of trastuzumab on the vasculature and its subsequent contribution to congestive heart failure.
Notes: Administration of trastuzumab inhibits HER2 receptors, which prevents dimerization with the neuregulin–HER4 complex. This subsequently causes a reduction in eNOS expression and NO bioavailability, along with a concomitant increase in ANG II and ROS. These processes culminate in endothelial dysfunction which is characterized by reduced vasodilatory capacity, enhanced vasoconstrictor tone, and endothelial injury. Endothelial dysfunction is a well-established causal factor for congestive heart failure because it increases systemic vascular resistance, afterload, and myocardial workload, but reduces coronary microvascular blood flow.
Abbreviations: ANG II, angiotensin II; eNOS, endothelial nitric oxide synthase; HER, human epidermal growth receptor; NO, nitric oxide; ROS, reactive oxygen species.
Abbreviations: ANG II, angiotensin II; eNOS, endothelial nitric oxide synthase; HER, human epidermal growth receptor; NO, nitric oxide; ROS, reactive oxygen species.
