TY - JOUR
T1 - Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model
AU - Gaar-Humphreys, Karen R
AU - Spanjersberg, Talitha C F
AU - Santarelli, Giorgia
AU - Grinwis, Guy C M
AU - Szatmári, Viktor
AU - Roelen, Bernard A J
AU - Vink, Aryan
AU - van Tintelen, J Peter
AU - Asselbergs, Folkert W
AU - Fieten, Hille
AU - Harakalova, Magdalena
AU - van Steenbeek, Frank G
N1 - Funding Information: Funding: T.C.F.S., J.P.v.T., F.W.A., M.H. and F.G.v.S. are supported by the Dutch Cardiovascular Alliance (DCVA) study Double-Dose [2020B005]. K.R.G.-H., F.W.A. and M.H. are supported by the ZonMW Open Competition study CONTRACT (09120012010018). J.P.v.T., F.W.A. and M.H. are supported by the Leducq Foundation study CURE-PLaN [18CVD01]. M.H. and F.G.v.S. are supported by the ERA-CVD study SCALE [2019T109]. H.F., J.P.v.T. and F.G.v.S. are supported by the LSH-TKI study Dog2Human [LSHM20093]. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - Cardiac disease is a leading cause of death for both humans and dogs. Genetic cardiomyopathies, including dilated cardiomyopathy (DCM), account for a proportion of these cases in both species. Patients may suffer from ventricular enlargement and systolic dysfunction resulting in congestive heart failure and ventricular arrhythmias with high risk for sudden cardiac death. Although canine DCM has similar disease progression and subtypes as in humans, only a few candidate genes have been found to be associated with DCM while the genetic background of human DCM has been more thoroughly studied. Additionally, experimental disease models using induced pluripotent stem cells have been widely adopted in the study of human genetic cardiomyopathy but have not yet been fully adapted for the in-depth study of canine genetic cardiomyopathies. The clinical presentation of DCM is extremely heterogeneous for both species with differences occurring based on sex predisposition, age of onset, and the rate of disease progression. Both genetic predisposition and environmental factors play a role in disease development which are identical in dogs and humans in contrast to other experimental animals. Interestingly, different dog breeds have been shown to develop distinct DCM phenotypes, and this presents a unique opportunity for modeling as there are multiple breed-specific models for DCM with less genetic variance than human DCM. A better understanding of DCM in dogs has the potential for improved selection for breeding and could lead to better overall care and treatment for human and canine DCM patients. At the same time, progress in research made for human DCM can have a positive impact on the care given to dogs affected by DCM. Therefore, this review will analyze the feasibility of canines as a naturally occurring bidirectional disease model for DCM in both species. The histopathology of the myocardium in canine DCM will be evaluated in three different breeds compared to control tissue, and the known genetics that contributes to both canine and human DCM will be summarized. Lastly, the prospect of canine iPSCs as a novel method to uncover the contributions of genetic variants to the pathogenesis of canine DCM will be introduced along with the applications for disease modeling and treatment.
AB - Cardiac disease is a leading cause of death for both humans and dogs. Genetic cardiomyopathies, including dilated cardiomyopathy (DCM), account for a proportion of these cases in both species. Patients may suffer from ventricular enlargement and systolic dysfunction resulting in congestive heart failure and ventricular arrhythmias with high risk for sudden cardiac death. Although canine DCM has similar disease progression and subtypes as in humans, only a few candidate genes have been found to be associated with DCM while the genetic background of human DCM has been more thoroughly studied. Additionally, experimental disease models using induced pluripotent stem cells have been widely adopted in the study of human genetic cardiomyopathy but have not yet been fully adapted for the in-depth study of canine genetic cardiomyopathies. The clinical presentation of DCM is extremely heterogeneous for both species with differences occurring based on sex predisposition, age of onset, and the rate of disease progression. Both genetic predisposition and environmental factors play a role in disease development which are identical in dogs and humans in contrast to other experimental animals. Interestingly, different dog breeds have been shown to develop distinct DCM phenotypes, and this presents a unique opportunity for modeling as there are multiple breed-specific models for DCM with less genetic variance than human DCM. A better understanding of DCM in dogs has the potential for improved selection for breeding and could lead to better overall care and treatment for human and canine DCM patients. At the same time, progress in research made for human DCM can have a positive impact on the care given to dogs affected by DCM. Therefore, this review will analyze the feasibility of canines as a naturally occurring bidirectional disease model for DCM in both species. The histopathology of the myocardium in canine DCM will be evaluated in three different breeds compared to control tissue, and the known genetics that contributes to both canine and human DCM will be summarized. Lastly, the prospect of canine iPSCs as a novel method to uncover the contributions of genetic variants to the pathogenesis of canine DCM will be introduced along with the applications for disease modeling and treatment.
KW - attenuated wavy fibers
KW - canine induced pluripotent stem cells
KW - cardiovascular
KW - fibrofatty infiltration
KW - human induced pluripotent stem cells
UR - http://www.scopus.com/inward/record.url?scp=85132967744&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ani12131679
DO - https://doi.org/10.3390/ani12131679
M3 - Review article
C2 - 35804579
SN - 2076-2615
VL - 12
JO - Animals
JF - Animals
IS - 13
M1 - 1679
ER -