Autophagy in load-induced heart disease.
The heart is a highly plastic organ capable of remodeling in response to changes in physiological or pathological demand. When workload increases, the heart compensates through hypertrophic growth of individual cardiomyocytes to increase cardiac output. However, sustained stress, such as occurs with hypertension or following myocardial infarction, triggers changes in sarcomeric protein composition and energy metabolism, loss of cardiomyocytes, ventricular dilation, reduced pump function, and ultimately heart failure. It has been known for some time that autophagy is active in cardiomyocytes, occurring at increased levels in disease. Yet the potential contribution of cardiomyocyte autophagy to ventricular remodeling and disease pathogenesis has only recently been explored. This latter fact stems largely from the recent emergence of tools to probe molecular mechanisms governing cardiac plasticity and to define the role of autophagic flux in the context of heart disease. In this chapter, we briefly review prominent mouse models useful in the study of load-induced heart disease and standard techniques used to assess whether a molecular or cellular event is adaptive or maladaptive. We then outline methods available for monitoring autophagic activity in the heart, providing detailed protocols for several techniques unique to working with heart and other striated muscles.
Zhu
Hongxin
H
Department of Internal Medicine (Cardiology), University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Rothermel
Beverly A
BA
Hill
Joseph A
JA
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002402:Cathepsin D / Q000378:metabolism; D006331:Heart Diseases / Q000378:metabolism*; D007150:Immunohistochemistry; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology; D052118:Lysosomal-Associated Membrane Protein 1
D002402:Cathepsin D; D051907:Lysosomal Membrane Proteins; D008869:Microtubule-Associated Proteins; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C480860:Map1lc3b protein, mouse