Cardioprotective engineering is an emerging bioengineering discipline aiming to develop engineering strategies to optimize cardioprotective actions against cardiac injuries and disorders. Although there exist innate cardioprotective mechanisms capable of supporting cardiomyocyte survival in response to an insult, not all these mechanisms are optimized in promptness and effectiveness, suggesting the necessity of cardioprotective engineering. Various cardioprotective strategies have been developed and used in experimental and clinical investigations; however, few of these strategies have exerted a significant clinical impact. There are two major challenges in cardioprotective engineering—understanding the innate cardioprotective mechanisms and developing engineering strategies for precise control of the types, levels, timing, and coordination of cardioprotective actions to facilitate recovery from injuries and disorders. Understanding the innate mechanisms is the foundation for developing cardioprotective engineering strategies. Here, ischemic myocardial injury is used as an example to demonstrate the concept of cardioprotective engineering.

References

1.
Liu
,
S. Q.
,
Ma
,
X. L.
,
Qin
,
G. J.
,
Liu
,
Q. P.
,
Li
,
Y. C.
, and
Wu
,
Y. H.
,
2015
, “
Trans-System Mechanisms Against Ischemic Myocardial Injury
,”
Comp. Physiol.
,
5
(
1
), pp.
167
192
.
2.
Cannan
,
W. J.
, and
Pederson
,
D. S.
,
2016
, “
Mechanisms and Consequences of Double-Strand DNA Break Formation in Chromatin
,”
J. Cell Physiol.
,
231
(
1
), pp.
3
14
.
3.
Jasin
,
M.
, and
Rothstein
,
R.
,
2013
, “
Repair of Strand Breaks by Homologous Recombination
,”
Cold Spring Harb. Perspect. Biol.
,
5
(
11
), p.
a012740
.
4.
Alvarado
,
A. S.
, and
Yamanaka
,
S.
,
2014
, “
Rethinking Differentiation: Stem Cells, Regeneration, and Plasticity
,”
Cell
,
157
(
1
), pp.
110
119
.
5.
Liu
,
S. Q.
,
2007
,
Bioregenerative Engineering: Principles and Applications
,
Wiley-Interscience
,
Hoboken, NJ
, pp.
420
455
.
6.
Tanaka
,
E.
, and
Reddien
,
P. W.
,
2011
, “
The Cellular Basis for Animal Regeneration
,”
Dev. Cell
,
21
(
1
), pp.
172
185
.
7.
Chen
,
L.
,
Deng
,
H.
,
Cui
,
H.
,
Fang
,
J.
,
Zuo
,
Z.
,
Deng
,
J.
,
Li
,
Y.
,
Wang
,
X.
, and
Zhao
,
L.
,
2018
, “
Inflammatory Responses and Inflammation-Associated Diseases in Organs
,”
Oncotarget
,
9
(
6
), pp.
7204
7218
.
8.
Rock
,
K. L.
, and
Kono
,
H.
,
2008
, “
The Inflammatory Response to Cell Death
,”
Annu. Rev. Pathol.
,
3
, pp.
99
126
.
9.
Gardiner
,
D. M.
,
2018
,
Regenerative Engineering and Developmental Biology: Principles and Applications
(CRC Press Series in Regenerative Engineering), 1st ed.,
CRC Press
,
Boca Raton, FL
.
10.
Laurencin
,
C. T.
, and
Khan
,
Y.
,
2018
,
Regenerative Engineering
, 1st ed.,
CRC Press
,
Boca Raton, FL
.
11.
Basson
,
M. A.
,
2012
, “
Signaling in Cell Differentiation and Morphogenesis
,”
Cold Spring Harb. Perspect. Biol.
,
4
(
6
), p.
a008151
.
12.
Duronio
,
R. J.
, and
Xiong
,
Y.
,
2013
, “
Signaling Pathways That Control Cell Proliferation
,”
Cold Spring Harb Perspect. Biol.
,
5
(
3
), p.
a008904
.
13.
Birnbaum
,
Y.
,
Hale
,
S. L.
, and
Kloner
,
R. A.
,
1997
, “
Ischemic Preconditioning at a Distance: Reduction of Myocardial Infarct Size by Partial Reduction of Blood Supply Combined With Rapid Stimulation of the Gastrocnemius Muscle in the Rabbit
,”
Circulation
,
96
(
5
), pp.
1641
1646
.
14.
Kloner
,
R. A.
, and
Rezkalla
,
S. H.
,
2006
, “
Preconditioning, Postconditioning and Their Application to Clinical Cardiology
,”
Cardiovasc. Res.
,
70
(
2
), pp.
297
307
.
15.
Murry
,
C. E.
,
Jennings
,
R. B.
, and
Reimer
,
K. A.
,
1986
, “
Preconditioning With Ischemia: A Delay of Lethal Cell Injury in Ischemic Myocardium
,”
Circulation
,
74
(
5
), pp.
1124
1136
.
16.
Granfeldt
,
A.
,
Lefer
,
D. J.
, and
Vinten-Johansen
,
J.
,
2009
, “
Protective Ischaemia in Patients: Preconditioning and Postconditioning
,”
Cardiovasc. Res.
,
83
(
2
), pp.
234
246
.
17.
Hausenloy
,
D. J.
, and
Yellon
,
D. M.
,
2011
, “
The Therapeutic Potential of Ischemic Conditioning: An Update
,”
Nat. Rev. Cardiol.
,
8
(
11
), pp.
619
629
.
18.
Schwarz
,
E. R.
,
Whyte
,
W. S.
, and
Kloner
,
R. A.
,
1997
, “
Ischemic Preconditioning
,”
Cur. Opin. Cardiol.
,
12
(
5
), pp.
475
481
.
19.
Vinten-Johansen
,
J.
,
Zhao
,
Z.
,
Jiang
,
R.
,
Zatta
,
A. J.
, and
Dobson
,
G. P.
,
2007
, “
Preconditioning and Postconditioning: Innate Cardioprotection From Ischemia Reperfusion Injury
,”
J. Appl. Physiol.
,
103
(
4
), pp.
1441
1448
.
20.
Yellon
,
D. M.
, and
Downey
,
J. M.
,
2003
, “
Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology
,”
Physiol. Rev.
,
83
(
4
), pp.
1113
1151
.
21.
Banai
,
S.
,
Shweiki
,
D.
,
Pinson
,
A.
,
Chandra
,
M.
,
Lazarovici
,
G.
, and
Keshet
,
E.
,
1994
, “
Upregulation of Vascular Endothelial Growth Factor Expression Induced by Myocardial Ischaemia: Implications for Coronary Angiogenesis
,”
Cardiovasc. Res.
,
28
(
8
), pp.
1176
1179
.
22.
Hashimoto
,
E.
,
Ogita
,
T.
,
Nakaoka
,
T.
,
Matsuoka
,
R.
,
Takao
,
A.
, and
Kira
,
Y.
,
1994
, “
Rapid Induction of Vascular Endothelial Growth Factor Expression by Transient Ischemia in Rat Heart
,”
Am. J. Physiol.
,
267
(
5 Pt. 2
), pp.
H1948
H1954
.
23.
Kawata
,
H.
,
Yoshida
,
K.-I.
,
Kawamoto
,
A.
,
Kurioka
,
H.
,
Takase
,
E.
,
Sasaki
,
Y.
,
Hatanaka
,
K.
,
Kobayashi
,
M.
,
Ueyama
,
T.
,
Hashimoto
,
T.
, and
Dohi
,
K.
,
2001
, “
Ischemic Preconditioning Upregulates Vascular Endothelial Growth Factor mRNA Expression and Neovascularization Via Nuclear Translocation of Protein Kinase C in the Rat Ischemic Myocardium
,”
Circ. Res.
,
88
(
7
), pp.
696
704
.
24.
Bell
,
S. P.
,
Sack
,
M. N.
,
Patel
,
A.
,
Opie
,
L. H.
, and
Yellon
,
D. M.
,
2000
, “
Opioid Receptor Stimulation Mimics Ischemic Preconditioning in Human Heart Muscle
,”
J. Am. Coll. Cardiol.
,
36
(
7
), pp.
2296
2302
.
25.
Bell
,
R. M.
, and
Yellon
,
D. M.
,
2003
, “
Bradykinin Limits Infarction When Administered as an Adjunct to Reperfusion in Mouse Heart: The Role of P18K, Akt and eNOS
,”
J. Mol. Cell Cardiol.
,
35
(
2
), pp.
185
193
.
26.
Fryer
,
R. M.
,
Hsu
,
A. K.
, and
Gross
,
G. J.
,
2001
, “
ERK and p38 MAP Kinase Activation Are Components of Opioid-Induced Delayed Cardioprotection
,”
Basic Res. Cardiol.
,
96
(
2
), pp.
136
142
.
27.
Goto
,
M.
,
Liu
,
Y.
,
Yang
,
X. M.
,
Ardell
,
J. L.
,
Cohen
,
M. V.
, and
Downey
,
J. M.
,
1995
, “
Role of Bradykinin in Protection of Ischemic Preconditioning in Rabbit Hearts
,”
Circ. Res.
,
77
(
3
), pp.
611
621
.
28.
Liu
,
G. S.
,
Thornton
,
J.
,
Van Winkle
,
D. M.
,
Stanley
,
A. W.
,
Olsson
,
R. A.
, and
Downey
,
J. M.
,
1991
, “
Protection Against Infarction Afforded by Preconditioning Is Mediated by A1 Adenosine Receptors in Rabbit Heart
,”
Circulation
,
84
(
1
), pp.
350
356
.
29.
Thornton
,
J. D.
,
Liu
,
G. S.
,
Olsson
,
R. A.
, and
Downey
,
J. M.
,
1992
, “
Intravenous Pretreatment With A1-Selective Adenosine Analogues Protects the Heart Against Infarction
,”
Circulation
,
85
(
2
), pp.
659
665
.
30.
Vinten-Johansen
,
J.
, and
Shi
,
W.
,
2011
, “
Preconditioning and Postconditioning: Current Knowledge, Knowledge Gaps, Barriers to Adoption, and Future Directions
,”
J. Cardiovasc. Pharmacol. Ther.
,
16
(
3–4
), pp.
260
266
.
31.
Ytrehus
,
K.
,
Liu
,
Y.
, and
Downey
,
J. M.
,
1994
, “
Preconditioning Protects Ischemic Rabbit Heart by Protein Kinase C Activation
,”
Am. J. Physiol.
,
266
(
3 Pt. 2
), pp.
H1145
H1152
.
32.
Liu
,
S. Q.
,
Tefft
,
B. J.
,
Roberts
,
D. T.
,
Zhang
,
L.-Q.
,
Ren
,
Y.
,
Li
,
Y. C.
,
Huang
,
Y.
,
Zhang
,
D.
,
Phillips
,
H. R.
, and
Wu
,
Y. H.
,
2012
, “
Cardioprotective Proteins Upregulated in the Liver in Response to Experimental Myocardial Ischemia
,”
Am. J. Physiol. Heart Circ. Physiol.
,
303
(
12
), pp.
H1446
1458
.
33.
Liu
,
S. Q.
,
Tefft
,
B. J.
,
Zhang
,
D.
,
Roberts
,
D.
,
Schuster
,
D. J.
, and
Wu
,
A.
,
2011
, “
Cardioprotective Mechanisms Activated in Response to Myocardial Ischemia
,”
MCB
,
8
(4), pp.
319
338
.http://www.techscience.com/doi/10.3970/mcb.2011.008.319.pdf
34.
Leevers
,
S. J.
,
Vanhaesebroeck
,
B.
, and
Waterfield
,
M. D.
,
1999
, “
Signalling Through Phosphoinositide 3-Kinases: The Lipids Take Centre Stage
,”
Cur. Opin. Cell Biol.
,
11
(
2
), pp.
219
225
.
35.
Datta
,
S. P.
,
Brunet
,
A.
, and
Greenberg
,
M. E.
,
1999
, “
Cellular Survival: A Play in Three Akts
,”
Genes Dev.
,
13
(
22
), pp.
2905
2927
.
36.
Torella
,
D.
,
Ellison
,
G. M.
,
Karakikes
,
I.
, and
Nadal-Ginard
,
B.
,
2007
, “
Growth Factor Mediated Cardiac Stem Cell Activation in Myocardial Regeneration
,”
Nat. Clin. Pract. Cardiovasc. Med.
,
4
(
S1
), pp.
S46
S51
.
37.
Liu
,
S. Q.
,
Roberts
,
D.
,
Kharitonenkov
,
A.
,
Li
,
Y. C.
,
Zhang
,
L.-Q.
, and
Wu
,
Y. H.
,
2013
, “
Cardioprotective Action of Fibroblast Growth Factor 21 Upregulated and Released From the Liver and Adipose Tissue in Experimental Myocardial Ischemia
,”
Sci. Rep.
,
3
, p.
2767
.
38.
Fournier
,
T.
,
Medjoubi-N
,
N.
, and
Porquet
,
D.
,
2000
, “
Alpha-1-Acid Glycoprotein
,”
Biochim. Biophys. Acta
,
1482
(
1–2
), pp.
157
171
.
39.
Muchitsch
,
E. M.
,
Teschner
,
W.
,
Linnau
,
Y.
, and
Pichler
,
L.
,
1996
, “
In Vivo Effect of α1-Acid Glycoprotein on Experimentally Enhanced Capillary Permeability in Guinea-Pigskin
,”
Arch. Int. Pharmacodyn. Ther.
,
331
(
3
), pp.
313
321
.
40.
Liu
,
H. M.
,
Takagaki
,
K.
, and
Schmid
,
K.
,
1988
, “
In Vitro Nerve-Growth-Promoting Activity of Human Plasma α1-Acid Glycoprotein
,”
J. Neurosci. Res.
,
20
(
1
), pp.
64
72
.
41.
Heinke
,
J.
,
Wehofsits
,
L.
,
Zhou
,
Q.
,
Zoeller
,
C.
,
Baar
,
K.-M.
,
Helbing
,
T.
,
Laib
,
A.
,
Augustin
,
H.
,
Bode
,
C.
,
Patterson
,
C.
, and
Moser
,
M.
,
2008
, “
BMPER Is an Endothelial Cell Regulator and Controls Bone Morphogenetic Protein-4–Dependent Angiogenesis
,”
Circ. Res.
,
103
(
8
), pp.
804
812
.
42.
Ikeya
,
M.
,
Kawada
,
M.
,
Kiyonari
,
H.
,
Sasai
,
N.
,
Nakao
,
K.
,
Furuta
,
Y.
, and
Sasai
,
Y.
,
2006
, “
Essential Pro-Bmp Roles of Crossveinless 2 in Mouse Organogenesis
,”
Development
,
133
(
22
), pp.
4463
4473
.
43.
Kelley
,
R.
,
Ren
,
R.
,
Pi
,
X.
,
Wu
,
Y.
,
Moreno
,
I.
,
Willis
,
M.
,
Moser
,
M.
,
Ross
,
M.
,
Podkowa
,
M.
,
Attisano
,
L.
, and
Patterson
,
C.
,
2009
, “
A Concentration-Dependent Endocytic Trap and Sink Mechanism Converts Bmper From an Activator to an Inhibitor of Bmp Signaling
,”
J. Cell Biol.
,
184
(
4
), pp.
597
560
.
44.
Kharitonenkov
,
A.
,
Shiyanova
,
T. L.
,
Koester
,
A.
,
Ford
,
A. M.
,
Micanovic
,
R.
,
Galbreath
,
E. J.
,
Sandusky
,
G. E.
,
Hammond
,
L. J.
,
Moyers
,
J. S.
,
Owens
,
R. A.
,
Gromada
,
J.
,
Brozinick
,
J. T.
,
Hawkins
,
E. D.
,
Wroblewski
,
V. J.
,
Li
,
D. S.
,
Mehrbod
,
F.
,
Jaskunas
,
S. R.
, and
Shanafelt
,
A. B.
,
2005
, “
FGF-21 as a Novel Metabolic Regulator
,”
J. Clin. Invest.
,
115
(
6
), pp.
1627
1635
.
45.
Nishimura
,
T.
,
Nakatake
,
Y.
,
Konishi
,
M.
, and
Itoh
,
N.
,
2000
, “
Identification of a Novel FGF, FGF-21, Preferentially Expressed in the Liver
,”
Biochim. Biophys. Acta.
,
1492
(
1
), pp.
203
206
.
46.
Ryde'n
,
M.
,
2009
, “
Fibroblast Growth Factor 21: An Overview From a Clinical Perspective
,”
Cell Mol. Life Sci.
,
66
(
13
), pp.
2067
2073
.
47.
Wente
,
W.
,
Efanov
,
A. M.
,
Brenner
,
M.
,
Kharitonenkov
,
A.
,
Köster
,
A.
,
Sandusky
,
G. E.
,
Sewing
,
S.
,
Treinies
,
I.
,
Zitzer
,
H.
, and
Gromada
,
J.
,
2006
, “
Fibroblast Growth Factor-21 Improves Pancreatic β-Cell Function and Survival by Activation of Extracellular Signal-Regulated Kinase 1/2 and Akt Signaling Pathways
,”
Diabetes
,
55
(
9
), pp.
2470
2478
.
48.
Dostalova
,
I.
,
Haluzikova
,
D.
, and
Haluzik
,
M.
,
2009
, “
Fibroblast Growth Factor 21: A Novel Metabolic Regulator With Potential Therapeutic Properties in Obesity/Type 2 Diabetes Mellitus
,”
Physiol. Res.
,
58
(
1
), pp.
1
7
.https://www.ncbi.nlm.nih.gov/pubmed/19331512
49.
Kharitonenkov
,
A.
,
2009
, “
FGFs and Metabolism
,”
Curr. Opin. Pharmacol.
,
9
(
6
), pp.
805
810
.
50.
Kharitonenkov
,
A.
, and
Larsen
,
P.
,
2011
, “
FGF21 Reloaded. Challenges of a Rapidly Growing Field
,”
Trends Enocrinol. Metab.
,
22
(
3
), pp.
81
86
.
51.
Badman
,
M. K.
,
Pissios
,
P.
,
Kennedy
,
A. R.
,
Koukos
,
G.
,
Flier
,
J. S.
, and
Maratos-Flier
,
E.
,
2007
, “
Hepatic Fibroblast Growth Factor 21 is Regulated by PPARa and is a Key Mediator of Hepatic Lipid Metabolism in Ketotic States
,”
Cell Metab.
,
5
(
6
), pp.
426
437
.
52.
Hotta
,
Y.
,
Nakamura
,
H.
,
Konishi
,
M.
,
Murata
,
Y.
,
Takagi
,
H.
,
Matsumura
,
S.
,
Inoue
,
K.
,
Fushiki
,
T.
, and
Itoh
,
N.
,
2009
, “
Fibroblast Growth Factor 21 Regulates Lipolysis in White Adipose Tissue But is Not Required for Ketogenesis and Triglyceride Clearance in Liver
,”
Endocrinology
,
150
(
10
), pp.
4625
4633
.
53.
Inagaki
,
T.
,
Dutchak
,
P.
,
Zhao
,
G.
,
Ding
,
X.
,
Gautron
,
L.
,
Parameswara
,
V.
,
Li
,
Y.
,
Goetz
,
R.
,
Mohammadi
,
M.
,
Esser
,
V.
,
Elmquist
,
J. K.
,
Gerard
,
R. D.
,
Burgess
,
S. C.
,
Hammer
,
R. E.
,
Mangelsdorf
,
D. J.
, and
Kliewer
,
S. A.
,
2007
, “
Endocrine Regulation of the Fasting Response by PPARa-Mediated Induction of Fibroblast Growth Factor 21
,”
Cell Metab.
,
5
(
6
), pp.
415
425
.
54.
Falls
,
D. L.
,
2003
, “
Neuregulins: Functions, Forms, and Signaling Strategies
,”
Exp. Cell Res.
,
284
(
1
), pp.
14
30
.
55.
Hayes
,
N. V. L.
,
Newsam
,
R. J.
,
Baines
,
A. J.
, and
Gullick
,
W. J.
,
2008
, “
Characterization of the Cell Membrane-Associated Products of the Neuregulin4 Gene
,”
Oncogene
,
27
(
5
), pp.
715
720
.
56.
Harari
,
D.
,
Tzahar
,
E.
,
Romano
,
J.
,
Shelly
,
M.
,
Pierce
,
J. H.
,
Andrews
,
G. C.
, and
Yarden
,
Y.
,
1999
, “
Neuregulin-4: A Novel Growth Factor That Acts Through the ErbB-4 Receptor Tyrosine Kinase
,”
Oncogene
,
18
(
17
), pp.
2681
2689
.
57.
Chinery
,
R.
,
Poulsom
,
R.
, and
Cox
,
H. M.
,
1996
, “
The Gene Encoding Mouse Intestinal Trefoil Factor: Structural Organization, Partial Sequence Analysis and Mapping to Murine Chromosome17q
,”
Gene
,
171
(
2
), pp.
249
253
.
58.
Sands
,
B. E.
, and
Podolsky
,
D. K.
,
1996
, “
The Trefoil Peptide Family
,”
Annu. Rev. Physiol.
,
58
, pp.
253
273
.
59.
Babyatsky
,
M. W.
,
de Beaumont
,
M.
,
Thim
,
L.
, and
Podolsky
,
D. K.
,
1996
, “
Oral Trefoil Peptides Protect Against Ethanol-and Indomethacin-Induced Gastric Injury in Rats
,”
Gastroenterology
,
110
(
2
), pp.
489
497
.
60.
Fazel
,
S. S.
,
Chen
,
L.
,
Angoulvant
,
D.
,
Li
,
S. H.
,
Weisel
,
R. D.
,
Keating
,
A.
, and
Li
,
R. K.
,
2008
, “
Activation of c-Kit is Necessary for Mobilization of Reparative Bone Marrow Progenitor Cells in Response to Cardiac Injury
,”
FASEB J.
,
22
(
3
), pp.
930
940
.
61.
Kucia
,
M.
,
Dawn
,
B.
,
Hunt
,
G.
,
Guo
,
Y.
,
Wysoczynski
,
M.
,
Majka
,
M.
,
Ratajczak
,
J.
,
Rezzoug
,
F.
,
Ildstad
,
S. T.
,
Bolli
,
R.
, and
Ratajczak
,
M. Z.
,
2004
, “
Cells Expressing Early Cardiac Markers Reside in the Bone Marrow and Are Mobilized Into the Peripheral Blood After Myocardial Infarction
,”
Circ. Res.
,
95
(
12
), pp.
1191
1199
.
62.
Ripa
,
R. S.
,
Jørgensen
,
E.
,
Wang
,
Y.
,
Thune
,
J. J.
,
Nilsson
,
J. C.
,
Søndergaard
,
L.
,
Johnsen
,
H. E.
,
Køber
,
L.
,
Grande
,
P.
, and
Kastrup
,
J.
,
2006
, “
Stem Cell Mobilization Induced by Subcutaneous Granulocyte-Colony Stimulating Factor to Improve Cardiac Regeneration After Acute ST-Elevation Myocardial Infarction: Result of the Double-Blind, Randomized, Placebo-Controlled in Myocardial Infarction (STEMMI) Trial
,”
Circulation
,
113
(
16
), pp.
1983
1992
.
63.
Swirski
,
F. K.
,
Nahrendorf
,
M.
,
Etzrodt
,
M.
,
Wildgruber
,
M.
,
Cortez-Retamozo
,
V.
,
Panizzi
,
P.
,
Figueiredo
,
J. L.
,
Kohler
,
R. H.
,
Chudnovskiy
,
A.
,
Waterman
,
P.
,
Aikawa
,
E.
,
Mempel
,
T. R.
,
Libby
,
P.
,
Weissleder
,
R.
, and
Pittet
,
M. J.
,
2009
, “
Identification of Splenic Reservoir Monocytes and Their Deployment to Inflammatory Sites
,”
Science
,
325
(
5940
), pp.
612
616
.
64.
Liu
,
S. Q.
,
Tefft
,
B. J.
,
Liu
,
C.
,
Zhang
,
B.
, and
Wu
,
Y. H.
,
2011
, “
Regulation of Hepatic Cell Mobilization in Experimental Myocardial Ischemia
,”
Cell Mol. Bioeng.
,
4
(
4
), pp.
693
707
.
65.
Shintani
,
S.
,
Murohara
,
T.
,
Ikeda
,
H.
,
Ueno
,
T.
,
Honma
,
T.
,
Katoh
,
A.
,
Sasaki
,
K.
,
Shimada
,
T.
,
Oike
,
Y.
, and
Imaizumi
,
T.
,
2001
, “
Mobilization of Endothelial Progenitor Cells in Patients With Acute Myocardial Infarction
,”
Circulation
,
103
(
23
), pp.
2776
2779
.
66.
Engelmann
,
M. G.
,
Theiss
,
H. D.
,
Hennig-Theiss
,
C.
,
Huber
,
A.
,
Wintersperger
,
B. J.
,
Werle-Ruedinger
,
A. E.
,
Schoenberg
,
S. O.
,
Steinbeck
,
G.
, and
Franz
,
W. M.
,
2006
, “
Autologous Bone Marrow Stem Cell Mobilization Induced by Granulocyte Colony-Stimulating Factor After Subacute ST-Segment Elevation Myocardial Infarction Undergoing Late Revascularization: Final Results From the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST- Elevation Myocardial Infarction) Trial
,”
J. Am. Coll. Cardiol.
,
48
(
8
), pp.
1712
1721
.
67.
Lombaert
,
I. M.
,
Wierenga
,
P. K.
,
Kok
,
T.
,
Kampinga
,
H. H.
,
de Haan
,
G.
, and
Coppes
,
R. P.
,
2006
, “
Mobilization of Bone Marrow Stem Cells by Granulocyte Colony-Stimulating Factor Ameliorates Radiation-Induced Damage to Salivary Glands
,”
Clin. Cancer Res.
,
12
(
6
), pp.
1804
1812
.
68.
Askari
,
A. T.
,
Unzek
,
S.
,
Popovic
,
Z. B.
,
Goldman
,
C. K.
,
Forudi
,
F.
,
Kiedrowski
,
M.
,
Rovner
,
A.
,
Ellis
,
S. G.
,
Thomas
,
J. D.
,
DiCorleto
,
P. E.
,
Topol
,
E. J.
, and
Penn
,
M. S.
,
2003
, “
Effect of Stromal-Cell-Derived Factor 1 on Stem-Cell Homing and Tissue Regeneration in Ischaemic Cardiomyopathy
,”
Lancet
,
362
(
9385
), pp.
697
703
.
69.
Hattori
,
K.
,
Heissig
,
B.
,
Tashiro
,
K.
,
Honjo
,
T.
,
Tateno
,
M.
,
Shieh
,
J. H.
,
Hackett
,
N. R.
,
Quitoriano
,
M. S.
,
Crystal
,
R. G.
,
Rafii
,
S.
, and
Moore
,
M. A.
,
2001
, “
Plasma Elevation of Stromal Cell-Derived Factor-1 Induces Mobilization of Mature and Immature Hematopoietic Progenitor and Stem Cells
,”
Blood
,
97
(
11
), pp.
3354
3360
.
70.
Asahara
,
T.
,
Takahashi
,
T.
,
Masuda
,
H.
,
Kalka
,
C.
,
Chen
,
D.
,
Iwaguro
,
H.
,
Inai
,
Y.
,
Silver
,
M.
, and
Isner
,
J. M.
,
1999
, “
VEGF Contributes to Postnatal Neovascularization by Mobilizing Bone Marrow-Derived Endothelial Progenitor Cells
,”
EMBO J.
,
18
(
14
), pp.
3964
3972
.
71.
Dunbar
,
C. E.
,
High
,
K. A.
,
Joung
,
J. K.
,
Kohn
,
D. B.
,
Ozawa
,
K.
, and
Sadelain
,
M.
,
2018
, “
Gene Therapy Comes of Age
,”
Science
,
359
(
6372
), p.
175
.
72.
Folino
,
A.
,
Accomasso
,
L.
,
Giachino
,
C.
,
Montarolo
,
P. G.
,
Losano
,
G.
,
Pagliaro
,
P.
, and
Rastaldo
,
R.
,
2018
, “
Apelin-Induced Cardioprotection Against Ischaemia/Reperfusion Injury: Roles of Epidermal Growth Factor and Src
,”
Acta Physiol.
,
222
(
2
), p.
12924
.
73.
House
,
S. L.
,
Branch
,
K.
,
Newman
,
G.
,
Doetschman
,
T.
, and
Schultz
,
J. J.
,
2005
, “
Cardioprotection Induced by Cardiac-Specific Overexpression of Fibroblast Growth Factor-2 Is Mediated by the MAPK Cascade
,”
Am. J. Physiol. Heart. Circ. Physiol.
,
289
(
5
), pp.
H2167
H2175
.
74.
Messadi
,
E.
,
Aloui
,
Z.
,
Belaidi
,
E.
,
Vincent
,
M. P.
,
Couture-Lepetit
,
E.
,
Waeckel
,
L.
,
Decorps
,
J.
,
Bouby
,
N.
,
Gasmi
,
A.
,
Karoui
,
H.
,
Ovize
,
M.
,
Alhenc-Gelas
,
F.
, and
Richer
,
C.
,
2014
, “
Cardioprotective Effect of VEGF and Venom VEGF-Like Protein in Acute Myocardial Ischemia in Mice: Effect on Mitochondrial Function
,”
J. Cardiovasc. Pharmacol.
,
63
(
3
), pp.
274
281
.
75.
Nakamura
,
T.
,
Mizuno
,
S.
,
Matsumoto
,
K.
,
Sawa
,
Y.
,
Matsuda
,
H.
, and
Nakamura
,
T.
,
2000
, “
Myocardial Protection From Ischemia/Reperfusion Injury by Endogenous and Exogenous HGF
,”
J. Clin. Invest.
,
106
(
12
), pp.
1511
1519
.
76.
Brar
,
B. K.
,
Stephanou
,
A.
,
Liao
,
Z.
,
O'Leary
,
R. M.
,
Pennica
,
D.
,
Yellon
,
D. M.
, and
Latchman
,
D. S.
,
2001
, “
Cardiotrophin-1 Can Protect Cardiac Myocytes From Injury When Added Both Prior to Simulated Ischaemia and at Reoxygenation
,”
Cardiovasc. Res.
,
51
(
2
), pp.
265
274
.
77.
Ghosh
,
S.
,
Ng
,
L. L.
,
Talwar
,
S.
,
Squire
,
I. B.
, and
Galiñanes
,
M.
,
2000
, “
Cardiotrophin-1 Protects the Human Myocardium From Ischemic Injury: Comparison With the First and Second Window of Protection by Ischemic Preconditioning
,”
Cardiovasc. Res.
,
48
(
3
), pp.
440
447
.
78.
Huang
,
C.
,
Gu
,
H.
,
Zhang
,
W.
,
Manukyan
,
M. C.
,
Shou
,
W.
, and
Wang
,
M.
,
2011
, “
SDF-1/CXCR4 Mediates Acute Protection of Cardiac Function Through Myocardial STAT3 Signaling Following Global Ischemia/Reperfusion Injury
,”
Am. J. Physiol. Heart Circ. Physiol.
,
301
(
4
), pp.
H1496
H1505
.
79.
Katz
,
M. G.
,
Swain
,
J. D.
,
Tomasulo
,
C. E.
,
Sumaroka
,
M.
,
Fargnoli
,
A.
, and
Bridges
,
C. R.
,
2011
, “
Current Strategies for Myocardial Gene Delivery
,”
J. Mol. Cell Cardiol.
,
50
(
5
), pp.
766
776
.
80.
Watts
,
J. K.
, and
Corey
,
D. R.
,
2012
, “
Gene Silencing by siRNAs and Antisense Oligonucleotides in the Laboratory and the Clinic
,”
J. Pathol.
,
226
(
2
), pp.
365
379
.
81.
Xia
,
H.
,
Mao
,
Q.
,
Paulson
,
H. L.
, and
Davidson
,
B. L.
,
2002
, “
siRNA-Mediated Gene Silencing In Vitro and In Vivo
,”
Nat. Biotech.
,
20
(
10
), pp.
1006
1010
.
82.
Napoli
,
C.
,
Lemieux
,
C.
, and
Jorgensen
,
R.
,
1990
, “
Introduction of a Chimeric Chalcone Synthase Gene Into Petunia Results in Reversible co-Suppression of Homologous Genes in Trans
,”
Plant Cell
,
2
(
4
), pp.
279
289
.
83.
van der Krol
,
A. R.
,
Mur
,
L. A.
,
Beld
,
M.
,
Moi
,
J. N. M.
, and
Stuitje
,
A. R.
,
1990
, “
Flavonoid Genes in Petunia: Addition of a Limited Number of Gene Copies May Lead to a Suppression of Gene Expression
,”
Plant Cell
,
2
(
4
), pp.
291
299
.
84.
Fire
,
A.
,
Xu
,
S.
,
Montgomery
,
M. K.
,
Kostas
,
S. A.
,
Driver
,
S. E.
, and
Mello
,
C. C.
,
1998
, “
Potent and Specific Genetic Interference by Double-Stranded RNA in Caenorhabditis elegans
,”
Nature
,
391
(
6669
), pp.
806
811
.
85.
Novina
,
C. D.
, and
Sharp
,
P. A.
,
2004
, “
The RNAi Revolution
,”
Nature
,
430
(
6996
), pp.
161
164
.
86.
Horvath
,
P.
, and
Barrangou
,
R.
,
2010
, “
CRISPR/Cas, the Immune System of Bacteria and Archaea
,”
Science
,
327
(
5962
), pp.
167
170
.
87.
Marraffini
,
L. A.
, and
Sontheimer
,
E. J.
,
2010
, “
CRISPR Interference: RNA-Directed Adaptive Immunity in Bacteria and Archaea
,”
Nat. Rev. Genet.
,
11
(
3
), pp.
181
190
.
88.
Deltcheva
,
E.
,
Chylinski
,
K.
,
Sharma
,
C. M.
,
Gonzales
,
K.
,
Chao
,
Y.
,
Pirzada
,
Z. A.
,
Eckert
,
M. R.
,
Vogel
,
J.
, and
Charpentier
,
E.
,
2011
, “
CRISPR RNA Maturation by Trans-Encoded Small RNA and Host Factor RNase III
,”
Nature
,
471
(
7340
), pp.
602
607
.
89.
Jinek
,
M.
,
Chylinski
,
K.
,
Fonfara
,
I.
,
Hauer
,
M.
,
Doudna
,
J. A.
, and
Charpentier
,
E.
,
2012
, “
A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity
,”
Science
,
337
(
6096
), pp.
816
821
.
90.
Gong
,
C.
,
Bongiorno
,
P.
,
Martins
,
A.
,
Stephanou
,
N. C.
,
Zhu
,
H.
,
Shuman
,
S.
, and
Glickman
,
M. S.
,
2005
, “
Mechanism of Nonhomologous End-Joining in Mycobacteria: A Low-Fidelity Repair System Driven by Ku, Ligase D and Ligase C
,”
Nat. Struct. Mol. Biol.
,
12
(
4
), pp.
304
312
.
91.
Overballe-Petersen
,
S.
,
Harms
,
K.
,
Orlando
,
L. A.
,
Mayar
,
J. V.
,
Rasmussen
,
S.
,
Dahl
,
T. W.
,
Rosing
,
M. T.
,
Poole
,
A. M.
,
Sicheritz-Ponten
,
T.
,
Brunak
,
S.
,
Inselmann
,
S.
,
de Vries
,
J.
,
Wackernagel
,
W.
,
Pybus
,
O. G.
,
Nielsen
,
R.
,
Johnsen
,
P. J.
,
Nielsen
,
K. M.
, and
Willerslev
,
E.
,
2013
, “
Bacterial Natural Transformation by Highly Fragmented and Damaged DNA
,”
PNAS
,
110
(
49
), pp.
19860
19865
.
92.
Abdel-Latif
,
A.
,
Bolli
,
R.
,
Tleyjeh
,
I. M.
,
Montori
,
V. M.
,
Perin
,
E. C.
,
Hornung
,
C. A.
,
Zuba-Surma
,
E. K.
,
Al-Mallah
,
M.
, and
Dawn
,
B.
,
2007
, “
Adult Bone Marrow-Derived Cells for Cardiac Repair: A Systematic Review and Meta-Analysis
,”
Arch. Intern. Med.
,
167
(
10
), pp.
989
997
.
93.
Carvalho
,
E.
,
Verma
,
P.
,
Hourigan
,
K.
, and
Banerjee
,
R.
,
2015
, “
Myocardial Infarction: Stem Cell Transplantation for Cardiac Regeneration
,”
Regen. Med.
,
10
(
8
), pp.
1025
1043
.
94.
Martin-Rendon
,
E.
,
Brunskill
,
S. J.
,
Hyde
,
C. J.
,
Stanworth
,
S. J.
,
Mathur
,
A.
, and
Watt
,
S. M.
,
2008
, “
Autologous Bone Marrow Stem Cells to Treat Acute Myocardial Infarction: A Systematic Review
,”
Eur. Heart J.
,
29
(
15
), pp.
1807
1818
.
95.
Domenech
,
M.
,
Polo-Corrales
,
L.
,
Ramirez-Vick
,
J. E.
, and
Freytes
,
D. O.
,
2016
, “
Tissue Engineering Strategies for Myocardial Regeneration: Acellular Versus Cellular Scaffolds?
Tissue Eng., Part B
,
22
(
6
), pp.
438
458
.
96.
Kaiser
,
N. J.
, and
Coulombe
,
K. L. K.
,
2015
, “
Physiologically Inspired Cardiac Scaffolds for Tailored In Vivo Function and Heart Regeneration
,”
Biomed. Mater.
,
10
(
3
), p.
034003
.
97.
Mannhardt
,
I.
,
Breckwoldt
,
K.
,
Letuffe-Brenière
,
D.
,
Schaaf
,
S.
,
Schulz
,
H.
,
Neuber
,
C.
,
Benzin
,
A.
,
Werner
,
T.
,
Eder
,
A.
,
Schulze
,
T.
,
Klampe
,
B.
,
Christ
,
T.
,
Hirt
,
M. N.
,
Huebner
,
N.
,
Moretti
,
A.
,
Eschenhagen
,
T.
, and
Hansen
,
A.
,
2016
, “
Human Engineered Heart Tissue: Analysis of Contractile Force
,”
Stem Cell Rep.
,
7
(
1
), pp.
29
42
.
98.
Wang
,
Z.
,
Lee
,
S. J.
,
Cheng
,
H.-J.
,
Yoo
,
J. J.
, and
Atala
,
A.
,
2018
, “
3D Bioprinted Functional and Contractile Cardiac Tissue Constructs
,”
Acta Biomater.
,
70
, pp.
48
56
.
You do not currently have access to this content.