Targeting Endoglin, an Auxiliary Transforming Growth Factor β Coreceptor, to Prevent Fibrosis and Heart Failure

Over the past 25 years, cardiovascular medicine has witnessed substantial progress in our understanding of the molecular pathogenesis, genetic causes, as well as the design of more efficacious therapeutic interventions. These advances have resulted in the dramatic reduction in the mortality of heart disease, especially in industrialized societies. Notwithstanding, both the prevalence and incidence of heart failure remain staggeringly high, posing new challenges and opportunities for prevention, diagnosis, and management. Defined as the inability of the heart, as a mechanical pump, to meet the peripheral metabolic demands, this syndrome has many complex pathophysiological interactions among systolic performance, ventricular relaxation, impairments of contractility, and diastolic dysfunction. Both acquired (ie, acute myocardial infarction) and genetic factors (mutations in genes encoding structural proteins) contribute to this clinical pathology, but the development of overt heart failure ominously increases morbidity and decreases life-span.Article see p 2728Among the remarkable successes of the late twentieth century has been the widespread practice and profound impact that β-adrenergic receptor antagonists have had on reducing the mortality and morbidity of heart failure.1 As reviewed recently by Michael Bristow,1 sobering lessons of this foregoing quintessential example of translational science were the emerging basic studies on adrenergic receptor pharmacobiology, the importance of adrenergic drive in heart failure pathogenesis, initial human studies on shifts from β1- to β2-adrenergic receptor subpopulations in the failing heart,2 and both observational and randomized clinical trials to guide evidence-based practice. Although aficionados used to the hype of the scientific news cycle are not easily persuaded, the ubiquitous claims of novel molecular targets for heart failure have not matched the disappointing and failure-prone pipeline in bringing new therapies to market. Without minimizing these efficacious drugs, there remain substantial unmet needs and opportunities, through intensive investments in basic and translational sciences, …