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  1. Article ; Online: Right ventricular cardiomyocyte expansion accompanies cardiac regeneration in newborn mice after large left ventricular infarcts.

    Hu, Tianyuan / Malek Mohammadi, Mona / Ebach, Fabian / Hesse, Michael / Kotlikoff, Michael I / Fleischmann, Bernd K

    JCI insight

    2024  Volume 9, Issue 5

    Abstract: Cauterization of the root of the left coronary artery (LCA) in the neonatal heart on postnatal day 1 (P1) resulted in large, reproducible lesions of the left ventricle (LV), and an attendant marked adaptive response in the right ventricle (RV). The ... ...

    Abstract Cauterization of the root of the left coronary artery (LCA) in the neonatal heart on postnatal day 1 (P1) resulted in large, reproducible lesions of the left ventricle (LV), and an attendant marked adaptive response in the right ventricle (RV). The response of both chambers to LV myocardial infarction involved enhanced cardiomyocyte (CM) division and binucleation, as well as LV revascularization, leading to restored heart function within 7 days post surgery (7 dps). By contrast, infarction of P3 mice resulted in cardiac scarring without a significant regenerative and adaptive response of the LV and the RV, leading to subsequent heart failure and death within 7 dps. The prominent RV myocyte expansion in P1 mice involved an acute increase in pulmonary arterial pressure and a unique gene regulatory response, leading to an increase in RV mass and preserved heart function. Thus, distinct adaptive mechanisms in the RV, such as CM proliferation and RV expansion, enable marked cardiac regeneration of the infarcted LV at P1 and full functional recovery.
    MeSH term(s) Animals ; Mice ; Heart Ventricles/pathology ; Myocytes, Cardiac/pathology ; Animals, Newborn ; Myocardial Infarction/pathology ; Regeneration
    Language English
    Publishing date 2024-02-06
    Publishing country United States
    Document type Journal Article
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.176281
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Public trust in the accreditation process.

    Kotlikoff, Michael I

    Journal of the American Veterinary Medical Association

    2015  Volume 246, Issue 8, Page(s) 835–836

    MeSH term(s) Conflict of Interest ; Education, Veterinary/standards ; Societies, Scientific/organization & administration ; Veterinary Medicine/organization & administration
    Language English
    Publishing date 2015-04-15
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 390811-2
    ISSN 1943-569X ; 0003-1488
    ISSN (online) 1943-569X
    ISSN 0003-1488
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  3. Article ; Online: Why the AVMA's Council on Education should be an independent entity.

    Kotlikoff, Michael I

    Journal of the American Veterinary Medical Association

    2015  Volume 246, Issue 6, Page(s) 599–600

    MeSH term(s) Education, Veterinary/organization & administration ; Education, Veterinary/standards ; Schools, Veterinary/standards ; Societies, Scientific/organization & administration ; United States ; Veterinarians/organization & administration ; Veterinary Medicine/organization & administration
    Language English
    Publishing date 2015-03-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 390811-2
    ISSN 1943-569X ; 0003-1488
    ISSN (online) 1943-569X
    ISSN 0003-1488
    DOI 10.2460/javma.246.6.599
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  4. Article ; Online: BACs to the future: new genetic models for cardiovascular discovery.

    Kotlikoff, Michael I

    Cardiovascular research

    2013  Volume 101, Issue 1, Page(s) 7–8

    MeSH term(s) Animals ; Atrial Natriuretic Factor/metabolism ; Cardiomegaly/metabolism ; Genes, Reporter ; Myocardial Infarction/metabolism ; Natriuretic Peptide, Brain/metabolism
    Chemical Substances Natriuretic Peptide, Brain (114471-18-0) ; Atrial Natriuretic Factor (85637-73-6)
    Language English
    Publishing date 2013-11-29
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvt266
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  5. Article: Genetically encoded Ca2+ indicators: using genetics and molecular design to understand complex physiology.

    Kotlikoff, Michael I

    The Journal of physiology

    2007  Volume 578, Issue Pt 1, Page(s) 55–67

    Abstract: This article reviews genetically encoded Ca2+ indicators (GECIs), with a focus on the use of these novel molecules in the context of understanding complex cell signalling in mammals, in vivo. The review focuses on the advantages and limitations of ... ...

    Abstract This article reviews genetically encoded Ca2+ indicators (GECIs), with a focus on the use of these novel molecules in the context of understanding complex cell signalling in mammals, in vivo. The review focuses on the advantages and limitations of specific GECI design strategies and the results of experiments in which these molecules have been expressed in transgenic mice, concentrating particularly on recent experiments from our laboratory in which physiological signalling could be monitored in vivo. Finally, newer strategies for effective genetic specification of GECIs are briefly reviewed.
    MeSH term(s) Animals ; Calcium Signaling/genetics ; Calcium Signaling/physiology ; Chromosomes, Artificial, Bacterial/genetics ; Fluorescence ; Fluorescence Resonance Energy Transfer ; Humans ; Indicators and Reagents ; Mice ; Mice, Transgenic ; Recombinant Proteins/genetics
    Chemical Substances Indicators and Reagents ; Recombinant Proteins
    Language English
    Publishing date 2007-01-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/jphysiol.2006.120212
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  6. Article ; Online: Calcium Signal Profiles in Vascular Endothelium from Cdh5-GCaMP8 and Cx40-GCaMP2 Mice.

    Chen, Yen Lin / Baker, Thomas M / Lee, Frank / Shui, Bo / Lee, Jane C / Tvrdik, Petr / Kotlikoff, Michael I / Sonkusare, Swapnil K

    Journal of vascular research

    2021  Volume 58, Issue 3, Page(s) 159–171

    Abstract: Introduction: Studies in Cx40-GCaMP2 mice, which express calcium biosensor GCaMP2 in the endothelium under connexin 40 promoter, have identified the unique properties of endothelial calcium signals. However, Cx40-GCaMP2 mouse is associated with a narrow ...

    Abstract Introduction: Studies in Cx40-GCaMP2 mice, which express calcium biosensor GCaMP2 in the endothelium under connexin 40 promoter, have identified the unique properties of endothelial calcium signals. However, Cx40-GCaMP2 mouse is associated with a narrow dynamic range and lack of signal in the venous endothelium. Recent studies have proposed many GCaMPs (GCaMP5/6/7/8) with improved properties although their performance in endothelium-specific calcium studies is not known.
    Methods: We characterized a newly developed mouse line that constitutively expresses GCaMP8 in the endothelium under the VE-cadherin (Cdh5-GCaMP8) promoter. Calcium signals through endothelial IP3 receptors and TRP vanilloid 4 (TRPV4) ion channels were recorded in mesenteric arteries (MAs) and veins from Cdh5-GCaMP8 and Cx40-GCaMP2 mice.
    Results: Cdh5-GCaMP8 mice showed lower baseline fluorescence intensity, higher dynamic range, and higher amplitudes of individual calcium signals than Cx40-GCaMP2 mice. Importantly, Cdh5-GCaMP8 mice enabled the first recordings of discrete calcium signals in the intact venous endothelium and revealed striking differences in IP3 receptor and TRPV4 channel calcium signals between MAs and mesenteric veins.
    Conclusion: Our findings suggest that Cdh5-GCaMP8 mice represent significant improvements in dynamic range, sensitivity for low-intensity signals, and the ability to record calcium signals in venous endothelium.
    MeSH term(s) Animals ; Antigens, CD/genetics ; Antigens, CD/metabolism ; Biosensing Techniques ; Cadherins/genetics ; Cadherins/metabolism ; Calcium/metabolism ; Calcium Signaling ; Calcium-Binding Proteins/genetics ; Calcium-Binding Proteins/metabolism ; Connexins/genetics ; Connexins/metabolism ; Endothelial Cells/metabolism ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Mesenteric Arteries/cytology ; Mesenteric Arteries/metabolism ; Mesenteric Veins/cytology ; Mesenteric Veins/metabolism ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Fluorescence ; Promoter Regions, Genetic ; TRPV Cation Channels/metabolism ; Gap Junction alpha-5 Protein ; Mice
    Chemical Substances Antigens, CD ; Cadherins ; Calcium-Binding Proteins ; Connexins ; GCaMP2 ; Inositol 1,4,5-Trisphosphate Receptors ; TRPV Cation Channels ; Trpv4 protein, mouse ; cadherin 5 ; Green Fluorescent Proteins (147336-22-9) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2021-03-11
    Publishing country Switzerland
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1105259-4
    ISSN 1423-0135 ; 1018-1172
    ISSN (online) 1423-0135
    ISSN 1018-1172
    DOI 10.1159/000514210
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    Zs.A 513: Show issues Location:
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  7. Article: Comment on "Do neonatal mouse hearts regenerate following heart apex resection"?

    Kotlikoff, Michael I / Hesse, Michael / Fleischmann, Bernd K

    Stem cell reports

    2014  Volume 3, Issue 1, Page(s) 2

    MeSH term(s) Aging/pathology ; Animals ; Heart/physiology ; Muscle Development ; Myocardial Infarction/pathology ; Myocytes, Cardiac/physiology ; Proto-Oncogene Proteins c-kit/metabolism ; Regeneration/physiology ; Stem Cells/cytology
    Chemical Substances Proto-Oncogene Proteins c-kit (EC 2.7.10.1)
    Language English
    Publishing date 2014-07-08
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2720528-9
    ISSN 2213-6711
    ISSN 2213-6711
    DOI 10.1016/j.stemcr.2014.06.010
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  8. Article ; Online: EDHF redux: EETs, TRPV4, and Ca2+ sparks.

    Kotlikoff, Michael I

    Circulation research

    2005  Volume 97, Issue 12, Page(s) 1209–1210

    MeSH term(s) 8,11,14-Eicosatrienoic Acid/analogs & derivatives ; 8,11,14-Eicosatrienoic Acid/pharmacology ; Animals ; Biological Factors/physiology ; Calcium/metabolism ; Calcium Signaling ; Humans ; Large-Conductance Calcium-Activated Potassium Channels/physiology ; Muscle, Smooth, Vascular/physiology ; Ryanodine Receptor Calcium Release Channel/physiology ; TRPV Cation Channels/physiology ; Vasodilation
    Chemical Substances Biological Factors ; Large-Conductance Calcium-Activated Potassium Channels ; Ryanodine Receptor Calcium Release Channel ; TRPV Cation Channels ; Trpv4 protein, rat ; endothelium-dependent hyperpolarization factor ; 11,12-epoxy-5,8,14-eicosatrienoic acid (5DOQ38R4UW) ; 8,11,14-Eicosatrienoic Acid (7324-41-6) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2005-12-09
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/01.RES.0000196741.99904.e4
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  9. Article ; Online: Concise review: The role of C-kit expressing cells in heart repair at the neonatal and adult stage.

    Hesse, Michael / Fleischmann, Bernd K / Kotlikoff, Michael I

    Stem cells (Dayton, Ohio)

    2014  Volume 32, Issue 7, Page(s) 1701–1712

    Abstract: Ischemic heart disease is the number one cause of morbidity and mortality in the developed world due to the inability of the heart to replace lost myocytes. The cause of postinfarction myogenic failure has been a subject of intense scientific ... ...

    Abstract Ischemic heart disease is the number one cause of morbidity and mortality in the developed world due to the inability of the heart to replace lost myocytes. The cause of postinfarction myogenic failure has been a subject of intense scientific investigation and much controversy. Recent data indicate a brief perinatal developmental window exists during which postinfarction myogenesis, and substantial heart regeneration, occurs. By contrast, repair of an equivalent injury of the adult heart results in prominent revascularization without myogenesis. Here, we review recent experiments on neonatal postinjury myogenesis, examine the mechanistic hypotheses of dedifferentiation and precursor expansion, and discuss experiments indicating that postinfarction revascularization derives primarily from cardiac vascular precursors. These data have profound consequences for the understanding of human heart repair, as they address the long standing question as to whether human postinfarction myogenic failure is due to the loss of precursors existent at the neonatal stage or to a context-dependent inhibition of these precursors within the infarct, and suggest strategies for the recapitulation of neonatal myogenic capacity and the augmentation of revascularization.
    MeSH term(s) Adult Stem Cells/physiology ; Animals ; Cell Dedifferentiation ; Coronary Vessels/physiopathology ; Heart/physiopathology ; Heart Diseases/physiopathology ; Humans ; Neovascularization, Physiologic ; Proto-Oncogene Proteins c-kit/metabolism ; Regeneration
    Chemical Substances Proto-Oncogene Proteins c-kit (EC 2.7.10.1)
    Language English
    Publishing date 2014-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1143556-2
    ISSN 1549-4918 ; 1066-5099
    ISSN (online) 1549-4918
    ISSN 1066-5099
    DOI 10.1002/stem.1696
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  10. Article ; Online: Local IP

    Longden, Thomas A / Mughal, Amreen / Hennig, Grant W / Harraz, Osama F / Shui, Bo / Lee, Frank K / Lee, Jane C / Reining, Shaun / Kotlikoff, Michael I / König, Gabriele M / Kostenis, Evi / Hill-Eubanks, David / Nelson, Mark T

    Science advances

    2021  Volume 7, Issue 30

    Abstract: Healthy brain function depends on the finely tuned spatial and temporal delivery of blood-borne nutrients to active neurons via the vast, dense capillary network. Here, using in vivo imaging in anesthetized mice, we reveal that brain capillary ... ...

    Abstract Healthy brain function depends on the finely tuned spatial and temporal delivery of blood-borne nutrients to active neurons via the vast, dense capillary network. Here, using in vivo imaging in anesthetized mice, we reveal that brain capillary endothelial cells control blood flow through a hierarchy of IP
    Language English
    Publishing date 2021-07-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abh0101
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