TY - JOUR
T1 - Chapter 17 Autophagy in Load-Induced Heart Disease
AU - Zhu, Hongxin
AU - Rothermel, Beverly A
AU - Hill, Joseph A
N1 - Funding Information:
This work was supported by grants from the Donald W. Reynolds Cardiovascular Clinical Research Center (JAH), NIH (HL‐72016, BAR; HL‐075173, JAH; HL‐080144, JAH), and AHA (0655202Y, BAR; 0640084N, JAH).
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=59649092589&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59649092589&partnerID=8YFLogxK
U2 - 10.1016/S0076-6879(08)04017-2
DO - 10.1016/S0076-6879(08)04017-2
M3 - Review article
C2 - 19216915
AN - SCOPUS:59649092589
SN - 0076-6879
VL - 453
SP - 343
EP - 363
JO - Methods in Enzymology
JF - Methods in Enzymology
IS - C
ER -