I am the head of Laboratory of Systems Biology and Professor in Biophysics at the Department of Cybernetics. I have defended by PhD in 2001 (Institute of Cybernetics at Tallinn University of Technology). After continuing my research in the Institute of Cybernetics (2002), I was a post-doctoral fellow at Université J. Fourier (2003-2004, Laboratory of Fundamental and Applied Bioenergetics, INSERM E0221) and Université Paris-Sud (2005, Faculté de Pharmacie, INSERM U446). After the post-doctorall studies, I returned to the Institute of Cybernetics and, with the help of Wellcome Trust International Senior Research Fellowship, started Laboratory of Systems Biology (2007).
Research Interests
My general research interests are linked with the physiology of the heart. I am interested in regulation of bioenergetics, its link to mechanics and electrophysiology. As a part of studies of regulation of intracellular processes in the heart, I am studying molecular movements and how intracellular communication is influenced by local environment as well as different diffusion obstacles in the heart muscle cells. For specific aims and interests, see the general homepage of Laboratory of Systems Biology.
Contact
e-mail: markov@sysbio.ioc.ee
Address:
Laboratory of Systems BiologyDepartment of Cybernetics
School of Science
Tallinn University of Technology
Akadeemia 15,
12618 Tallinn
ESTONIA
phone: (+372) 620 4169
Last Publications
4906808
BJ28HM24
Vendelin
items
1
apa
5
date
desc
https://sysbio.ioc.ee/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22instance%22%3A%22zotpress-bbe240cb37a931595df6dc66f57b6631%22%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22DK5WCEMD%22%2C%22library%22%3A%7B%22id%22%3A4906808%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Risti%20et%20al.%22%2C%22parsedDate%22%3A%222023-04-12%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ERisti%2C%20R.%2C%20Gunn%2C%20K.%20H.%2C%20Hiis-Hommuk%2C%20K.%2C%20Seeba%2C%20N.-N.%2C%20Karimi%2C%20H.%2C%20Villo%2C%20L.%2C%20Vendelin%2C%20M.%2C%20Neher%2C%20S.%20B.%2C%20%26amp%3B%20L%26%23xF5%3Bokene%2C%20A.%20%282023%29.%20Combined%20action%20of%20albumin%20and%20heparin%20regulates%20lipoprotein%20lipase%20oligomerization%2C%20stability%2C%20and%20ligand%20interactions.%20%3Ci%3EPLOS%20ONE%3C%5C%2Fi%3E%2C%20%3Ci%3E18%3C%5C%2Fi%3E%284%29%2C%20e0283358.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1371%5C%2Fjournal.pone.0283358%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1371%5C%2Fjournal.pone.0283358%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Combined%20action%20of%20albumin%20and%20heparin%20regulates%20lipoprotein%20lipase%20oligomerization%2C%20stability%2C%20and%20ligand%20interactions%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Robert%22%2C%22lastName%22%3A%22Risti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kathryn%20H.%22%2C%22lastName%22%3A%22Gunn%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kristofer%22%2C%22lastName%22%3A%22Hiis-Hommuk%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Natjan-Naatan%22%2C%22lastName%22%3A%22Seeba%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hamed%22%2C%22lastName%22%3A%22Karimi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ly%22%2C%22lastName%22%3A%22Villo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marko%22%2C%22lastName%22%3A%22Vendelin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Saskia%20B.%22%2C%22lastName%22%3A%22Neher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Aivar%22%2C%22lastName%22%3A%22L%5Cu00f5okene%22%7D%5D%2C%22abstractNote%22%3A%22Lipoprotein%20lipase%20%28LPL%29%2C%20a%20crucial%20enzyme%20in%20the%20intravascular%20hydrolysis%20of%20triglyceride-rich%20lipoproteins%2C%20is%20a%20potential%20drug%20target%20for%20the%20treatment%20of%20hypertriglyceridemia.%20The%20activity%20and%20stability%20of%20LPL%20are%20influenced%20by%20a%20complex%20ligand%20network.%20Previous%20studies%20performed%20in%20dilute%20solutions%20suggest%20that%20LPL%20can%20appear%20in%20various%20oligomeric%20states.%20However%2C%20it%20was%20not%20known%20how%20the%20physiological%20environment%2C%20that%20is%20blood%20plasma%2C%20affects%20the%20action%20of%20LPL.%20In%20the%20current%20study%2C%20we%20demonstrate%20that%20albumin%2C%20the%20major%20protein%20component%20in%20blood%20plasma%2C%20has%20a%20significant%20impact%20on%20LPL%20stability%2C%20oligomerization%2C%20and%20ligand%20interactions.%20The%20effects%20induced%20by%20albumin%20could%20not%20solely%20be%20reproduced%20by%20the%20macromolecular%20crowding%20effect.%20Stabilization%2C%20isothermal%20titration%20calorimetry%2C%20and%20surface%20plasmon%20resonance%20studies%20revealed%20that%20albumin%20binds%20to%20LPL%20with%20affinity%20sufficient%20to%20form%20a%20complex%20in%20both%20the%20interstitial%20space%20and%20the%20capillaries.%20Negative%20stain%20transmission%20electron%20microscopy%20and%20raster%20image%20correlation%20spectroscopy%20showed%20that%20albumin%2C%20like%20heparin%2C%20induced%20reversible%20oligomerization%20of%20LPL.%20However%2C%20the%20albumin%20induced%20oligomers%20were%20structurally%20different%20from%20heparin-induced%20filament-like%20LPL%20oligomers.%20An%20intriguing%20observation%20was%20that%20no%20oligomers%20of%20either%20type%20were%20formed%20in%20the%20simultaneous%20presence%20of%20albumin%20and%20heparin.%20Our%20data%20also%20suggested%20that%20the%20oligomer%20formation%20protected%20LPL%20from%20the%20inactivation%20by%20its%20physiological%20regulator%20angiopoietin-like%20protein%204.%20The%20concentration%20of%20LPL%20and%20its%20environment%20could%20influence%20whether%20LPL%20follows%20irreversible%20inactivation%20and%20aggregation%20or%20reversible%20LPL%20oligomer%20formation%2C%20which%20might%20affect%20interactions%20with%20various%20ligands%20and%20drugs.%20In%20conclusion%2C%20the%20interplay%20between%20albumin%20and%20heparin%20could%20provide%20a%20mechanism%20for%20ensuring%20the%20dissociation%20of%20heparan%20sulfate-bound%20LPL%20oligomers%20into%20active%20LPL%20upon%20secretion%20into%20the%20interstitial%20space.%22%2C%22date%22%3A%22Apr%2012%2C%202023%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1371%5C%2Fjournal.pone.0283358%22%2C%22ISSN%22%3A%221932-6203%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fjournals.plos.org%5C%2Fplosone%5C%2Farticle%3Fid%3D10.1371%5C%2Fjournal.pone.0283358%22%2C%22collections%22%3A%5B%22BJ28HM24%22%5D%2C%22dateModified%22%3A%222023-05-01T12%3A00%3A14Z%22%7D%7D%2C%7B%22key%22%3A%22N2N5ACYK%22%2C%22library%22%3A%7B%22id%22%3A4906808%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Laasmaa%20et%20al.%22%2C%22parsedDate%22%3A%222023%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELaasmaa%2C%20M.%2C%20Branovets%2C%20J.%2C%20Stolova%2C%20J.%2C%20Shen%2C%20X.%2C%20R%26%23xE4%3Btsepso%2C%20T.%2C%20Balodis%2C%20M.%20J.%2C%20Grahv%2C%20C.%2C%20Hendrikson%2C%20E.%2C%20Louch%2C%20W.%20E.%2C%20Birkedal%2C%20R.%2C%20%26amp%3B%20Vendelin%2C%20M.%20%282023%29.%20Cardiomyocytes%20from%20female%20compared%20to%20male%20mice%20have%20larger%20ryanodine%20receptor%20clusters%20and%20higher%20calcium%20spark%20frequency.%20%3Ci%3EThe%20Journal%20of%20Physiology%3C%5C%2Fi%3E%2C%20%3Ci%3E601%3C%5C%2Fi%3E%2818%29%2C%204033%26%23x2013%3B4052.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1113%5C%2FJP284515%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1113%5C%2FJP284515%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Cardiomyocytes%20from%20female%20compared%20to%20male%20mice%20have%20larger%20ryanodine%20receptor%20clusters%20and%20higher%20calcium%20spark%20frequency%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Martin%22%2C%22lastName%22%3A%22Laasmaa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jelena%22%2C%22lastName%22%3A%22Branovets%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jekaterina%22%2C%22lastName%22%3A%22Stolova%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xin%22%2C%22lastName%22%3A%22Shen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Triinu%22%2C%22lastName%22%3A%22R%5Cu00e4tsepso%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mihkel%20Jaan%22%2C%22lastName%22%3A%22Balodis%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C%5Cu00e4rolin%22%2C%22lastName%22%3A%22Grahv%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Eliise%22%2C%22lastName%22%3A%22Hendrikson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22William%20Edward%22%2C%22lastName%22%3A%22Louch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rikke%22%2C%22lastName%22%3A%22Birkedal%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marko%22%2C%22lastName%22%3A%22Vendelin%22%7D%5D%2C%22abstractNote%22%3A%22Sex%20differences%20in%20cardiac%20physiology%20are%20receiving%20increased%20attention%20as%20it%20has%20become%20clear%20that%20men%20and%20women%20have%20different%20aetiologies%20of%20cardiac%20disease%20and%20require%20different%20treatments.%20There%20are%20experimental%20data%20suggesting%20that%20male%20cardiomyocytes%20exhibit%20larger%20Ca2%2B%20transients%20due%20to%20larger%20Ca2%2B%20sparks%20and%20a%20higher%20excitation%5Cu2013contraction%20coupling%20gain%3B%20in%20addition%2C%20they%20exhibit%20a%20larger%20response%20to%20adrenergic%20stimulation%20with%20isoprenaline%20%28ISO%29.%20Here%2C%20we%20studied%20whether%20there%20are%20sex%20differences%20relating%20to%20structural%20organization%20of%20the%20transverse%20tubular%20network%20and%20ryanodine%20receptors%20%28RyRs%29.%20Surprisingly%2C%20we%20found%20that%20female%20cardiomyocytes%20exhibited%20a%20higher%20spark%20frequency%20in%20a%20range%20of%20spark%20magnitudes.%20While%20overall%20RyR%20expression%20and%20phosphorylation%20were%20the%20same%2C%20female%20cardiomyocytes%20had%20larger%20but%20fewer%20RyR%20clusters.%20The%20density%20of%20transverse%20t-tubules%20was%20the%20same%2C%20but%20male%20cardiomyocytes%20had%20more%20longitudinal%20t-tubules.%20The%20Ca2%2B%20transients%20were%20similar%20in%20male%20and%20female%20cardiomyocytes%20under%20control%20conditions%20and%20in%20the%20presence%20of%20ISO.%20The%20synchrony%20of%20the%20Ca2%2B%20transients%20was%20similar%20between%20sexes%20as%20well.%20Overall%2C%20our%20data%20suggest%20subtle%20sex%20differences%20in%20the%20Ca2%2B%20influx%20and%20efflux%20pathways%20and%20their%20response%20to%20ISO%2C%20but%20these%20differences%20are%20balanced%2C%20resulting%20in%20similar%20Ca2%2B%20transients%20in%20field-stimulated%20male%20and%20female%20cardiomyocytes.%20The%20higher%20spark%20frequency%20in%20female%20cardiomyocytes%20is%20related%20to%20the%20organization%20of%20RyRs%20into%20larger%2C%20but%20fewer%20clusters.%20Key%20points%20During%20a%20heartbeat%2C%20the%20force%20of%20contraction%20depends%20on%20the%20amplitude%20of%20the%20calcium%20transient%2C%20which%20in%20turn%20depends%20on%20the%20amount%20of%20calcium%20released%20as%20calcium%20sparks%20through%20ryanodine%20receptors%20in%20the%20sarcoplasmic%20reticulum.%20Previous%20studies%20suggest%20that%20cardiomyocytes%20from%20male%20compared%20to%20female%20mice%20exhibit%20larger%20calcium%20sparks%2C%20larger%20sarcoplasmic%20reticulum%20calcium%20release%20and%20greater%20response%20to%20adrenergic%20stimulation%20triggering%20a%20fight-or-flight%20response.%20In%20contrast%2C%20we%20show%20that%20cardiomyocytes%20from%20female%20mice%20have%20a%20higher%20spark%20frequency%20during%20adrenergic%20stimulation%20and%20similar%20spark%20morphology.%20The%20higher%20spark%20frequency%20is%20related%20to%20the%20organization%20of%20ryanodine%20receptors%20into%20fewer%2C%20but%20larger%20clusters%20in%20female%20compared%20to%20male%20mouse%20cardiomyocytes.%20Despite%20subtle%20sex%20differences%20in%20cardiomyocyte%20structure%20and%20calcium%20fluxes%2C%20the%20differences%20are%20balanced%2C%20leading%20to%20similar%20calcium%20transients%20in%20cardiomyocytes%20from%20male%20and%20female%20mice.%22%2C%22date%22%3A%222023%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1113%5C%2FJP284515%22%2C%22ISSN%22%3A%221469-7793%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fonlinelibrary.wiley.com%5C%2Fdoi%5C%2Fabs%5C%2F10.1113%5C%2FJP284515%22%2C%22collections%22%3A%5B%22BJ28HM24%22%5D%2C%22dateModified%22%3A%222023-09-16T17%3A23%3A25Z%22%7D%7D%2C%7B%22key%22%3A%22ZKA9DUTB%22%2C%22library%22%3A%7B%22id%22%3A4906808%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Birkedal%20et%20al.%22%2C%22parsedDate%22%3A%222022-11-21%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EBirkedal%2C%20R.%2C%20Laasmaa%2C%20M.%2C%20Branovets%2C%20J.%2C%20%26amp%3B%20Vendelin%2C%20M.%20%282022%29.%20Ontogeny%20of%20cardiomyocytes%3A%20ultrastructure%20optimization%20to%20meet%20the%20demand%20for%20tight%20communication%20in%20excitation%26%23x2013%3Bcontraction%20coupling%20and%20energy%20transfer.%20%3Ci%3EPhilosophical%20Transactions%20of%20the%20Royal%20Society%20B%3A%20Biological%20Sciences%3C%5C%2Fi%3E%2C%20%3Ci%3E377%3C%5C%2Fi%3E%281864%29%2C%2020210321.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1098%5C%2Frstb.2021.0321%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1098%5C%2Frstb.2021.0321%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Ontogeny%20of%20cardiomyocytes%3A%20ultrastructure%20optimization%20to%20meet%20the%20demand%20for%20tight%20communication%20in%20excitation%5Cu2013contraction%20coupling%20and%20energy%20transfer%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rikke%22%2C%22lastName%22%3A%22Birkedal%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Martin%22%2C%22lastName%22%3A%22Laasmaa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jelena%22%2C%22lastName%22%3A%22Branovets%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marko%22%2C%22lastName%22%3A%22Vendelin%22%7D%5D%2C%22abstractNote%22%3A%22The%20ontogeny%20of%20the%20heart%20describes%20its%20development%20from%20the%20fetal%20to%20the%20adult%20stage.%20In%20newborn%20mammals%2C%20blood%20pressure%20and%20thus%20cardiac%20performance%20are%20relatively%20low.%20The%20cardiomyocytes%20are%20thin%2C%20and%20with%20a%20central%20core%20of%20mitochondria%20surrounded%20by%20a%20ring%20of%20myofilaments%2C%20while%20the%20sarcoplasmic%20reticulum%20%28SR%29%20is%20sparse.%20During%20development%2C%20as%20blood%20pressure%20and%20performance%20increase%2C%20the%20cardiomyocytes%20become%20more%20packed%20with%20structures%20involved%20in%20excitation%5Cu2013contraction%20%28e-c%29%20coupling%20%28SR%20and%20myofilaments%29%20and%20the%20generation%20of%20ATP%20%28mitochondria%29%20to%20fuel%20the%20contraction.%20In%20parallel%2C%20the%20e-c%20coupling%20relies%20increasingly%20on%20calcium%20fluxes%20through%20the%20SR%2C%20while%20metabolism%20relies%20increasingly%20on%20fatty%20acid%20oxidation.%20The%20development%20of%20transverse%20tubules%20and%20SR%20brings%20channels%20and%20transporters%20interacting%20via%20calcium%20closer%20to%20each%20other%20and%20is%20crucial%20for%20e-c%20coupling.%20However%2C%20for%20energy%20transfer%2C%20it%20may%20seem%20counterintuitive%20that%20the%20increased%20structural%20density%20restricts%20the%20overall%20ATP%5C%2FADP%20diffusion.%20In%20this%20review%2C%20we%20discuss%20how%20this%20is%20because%20of%20the%20organization%20of%20all%20these%20structures%20forming%20modules.%20Although%20the%20overall%20diffusion%20across%20modules%20is%20more%20restricted%2C%20the%20energy%20transfer%20within%20modules%20is%20fast.%20A%20few%20studies%20suggest%20that%20in%20failing%20hearts%20this%20modular%20design%20is%20disrupted%2C%20and%20this%20may%20compromise%20intracellular%20energy%20transfer.%5Cn%5CnThis%20article%20is%20part%20of%20the%20theme%20issue%20%5Cu2018The%20cardiomyocyte%3A%20new%20revelations%20on%20the%20interplay%20between%20architecture%20and%20function%20in%20growth%2C%20health%2C%20and%20disease%5Cu2019.%22%2C%22date%22%3A%222022-11-21%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1098%5C%2Frstb.2021.0321%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Froyalsocietypublishing.org%5C%2Fdoi%5C%2F10.1098%5C%2Frstb.2021.0321%22%2C%22collections%22%3A%5B%22BJ28HM24%22%5D%2C%22dateModified%22%3A%222023-01-09T11%3A50%3A21Z%22%7D%7D%2C%7B%22key%22%3A%22TJ723E7D%22%2C%22library%22%3A%7B%22id%22%3A4906808%7D%2C%22meta%22%3A%7B%22lastModifiedByUser%22%3A%7B%22id%22%3A317201%2C%22username%22%3A%22marko.vendelin%22%2C%22name%22%3A%22Marko%20Vendelin%22%2C%22links%22%3A%7B%22alternate%22%3A%7B%22href%22%3A%22https%3A%5C%2F%5C%2Fwww.zotero.org%5C%2Fmarko.vendelin%22%2C%22type%22%3A%22text%5C%2Fhtml%22%7D%7D%7D%2C%22creatorSummary%22%3A%22Branovets%20et%20al.%22%2C%22parsedDate%22%3A%222021-02-01%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EBranovets%2C%20J.%2C%20Karro%2C%20N.%2C%20Barsunova%2C%20K.%2C%20Laasmaa%2C%20M.%2C%20Lygate%2C%20C.%20A.%2C%20Vendelin%2C%20M.%2C%20%26amp%3B%20Birkedal%2C%20R.%20%282021%29.%20Cardiac%20expression%20and%20location%20of%20hexokinase%20changes%20in%20a%20mouse%20model%20of%20pure%20creatine%20deficiency.%20%3Ci%3EAmerican%20Journal%20of%20Physiology-Heart%20and%20Circulatory%20Physiology%3C%5C%2Fi%3E%2C%20%3Ci%3E320%3C%5C%2Fi%3E%282%29%2C%20H613%26%23x2013%3BH629.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1152%5C%2Fajpheart.00188.2020%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1152%5C%2Fajpheart.00188.2020%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Cardiac%20expression%20and%20location%20of%20hexokinase%20changes%20in%20a%20mouse%20model%20of%20pure%20creatine%20deficiency%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jelena%22%2C%22lastName%22%3A%22Branovets%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Niina%22%2C%22lastName%22%3A%22Karro%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Karina%22%2C%22lastName%22%3A%22Barsunova%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Martin%22%2C%22lastName%22%3A%22Laasmaa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Craig%20A.%22%2C%22lastName%22%3A%22Lygate%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marko%22%2C%22lastName%22%3A%22Vendelin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rikke%22%2C%22lastName%22%3A%22Birkedal%22%7D%5D%2C%22abstractNote%22%3A%22Creatine%20kinase%20%28CK%29%20is%20considered%20the%20main%20phosphotransfer%20system%20in%20the%20heart%2C%20important%20for%20overcoming%20diffusion%20restrictions%20and%20regulating%20mitochondrial%20respiration.%20It%20is%20substrate%20limited%20in%20creatine-deficient%20mice%20lacking%20l-arginine%3Aglycine%20amidinotransferase%20%28AGAT%29%20or%20guanidinoacetate%20N-methyltranferase%20%28GAMT%29.%20Our%20aim%20was%20to%20determine%20the%20expression%2C%20activity%2C%20and%20mitochondrial%20coupling%20of%20hexokinase%20%28HK%29%20and%20adenylate%20kinase%20%28AK%29%2C%20as%20these%20represent%20alternative%20energy%20transfer%20systems.%20In%20permeabilized%20cardiomyocytes%2C%20we%20assessed%20how%20much%20endogenous%20ADP%20generated%20by%20HK%2C%20AK%2C%20or%20CK%20stimulated%20mitochondrial%20respiration%20and%20how%20much%20was%20channeled%20to%20mitochondria.%20In%20whole%20heart%20homogenates%2C%20and%20cytosolic%20and%20mitochondrial%20fractions%2C%20we%20measured%20the%20activities%20of%20AK%2C%20CK%2C%20and%20HK.%20Lastly%2C%20we%20assessed%20the%20expression%20of%20the%20major%20HK%2C%20AK%2C%20and%20CK%20isoforms.%20Overall%2C%20respiration%20stimulated%20by%20HK%2C%20AK%2C%20and%20CK%20was%20%5Cu223c25%2C%2090%2C%20and%2080%25%2C%20respectively%2C%20of%20the%20maximal%20respiration%20rate%2C%20and%20%5Cu223c20%2C%200%2C%20and%2025%25%2C%20respectively%2C%20was%20channeled%20to%20the%20mitochondria.%20The%20activity%2C%20distribution%2C%20and%20expression%20of%20HK%2C%20AK%2C%20and%20CK%20did%20not%20change%20in%20GAMT%20knockout%20%28KO%29%20mice.%20In%20AGAT%20KO%20mice%2C%20we%20found%20no%20changes%20in%20AK%2C%20but%20we%20found%20a%20higher%20HK%20activity%20in%20the%20mitochondrial%20fraction%2C%20greater%20expression%20of%20HK%20I%2C%20but%20a%20lower%20stimulation%20of%20respiration%20by%20HK.%20Our%20findings%20suggest%20that%20mouse%20hearts%20depend%20less%20on%20phosphotransfer%20systems%20to%20facilitate%20ADP%20flux%20across%20the%20mitochondrial%20membrane.%20In%20AGAT%20KO%20mice%2C%20which%20are%20a%20model%20of%20pure%20creatine%20deficiency%2C%20the%20changes%20in%20HK%20may%20reflect%20changes%20in%20metabolism%20as%20well%20as%20influence%20mitochondrial%20regulation%20and%20reactive%20oxygen%20species%20production.NEW%20%26%20NOTEWORTHY%20In%20creatine-deficient%20AGAT%5Cu2212%5C%2F%5Cu2212%20and%20GAMT%5Cu2212%5C%2F%5Cu2212%20mice%2C%20the%20myocardial%20creatine%20kinase%20system%20is%20substrate%20limited.%20It%20is%20unknown%20whether%20subcellular%20localization%20and%20mitochondrial%20ADP%20channeling%20by%20hexokinase%20and%20adenylate%20kinase%20may%20compensate%20as%20alternative%20phosphotransfer%20systems.%20Our%20results%20show%20no%20changes%20in%20adenylate%20kinase%2C%20which%20is%20the%20main%20alternative%20to%20creatine%20kinase%20in%20heart.%20However%2C%20we%20found%20increased%20expression%20and%20activity%20of%20hexokinase%20I%20in%20AGAT%5Cu2212%5C%2F%5Cu2212%20cardiomyocytes.%20This%20could%20affect%20mitochondrial%20regulation%20and%20reactive%20oxygen%20species%20production.%22%2C%22date%22%3A%22February%201%2C%202021%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1152%5C%2Fajpheart.00188.2020%22%2C%22ISSN%22%3A%220363-6135%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fjournals.physiology.org%5C%2Fdoi%5C%2Ffull%5C%2F10.1152%5C%2Fajpheart.00188.2020%22%2C%22collections%22%3A%5B%22BJ28HM24%22%5D%2C%22dateModified%22%3A%222023-05-08T11%3A04%3A25Z%22%7D%7D%2C%7B%22key%22%3A%224R2IADLH%22%2C%22library%22%3A%7B%22id%22%3A4906808%7D%2C%22meta%22%3A%7B%22lastModifiedByUser%22%3A%7B%22id%22%3A317201%2C%22username%22%3A%22marko.vendelin%22%2C%22name%22%3A%22Marko%20Vendelin%22%2C%22links%22%3A%7B%22alternate%22%3A%7B%22href%22%3A%22https%3A%5C%2F%5C%2Fwww.zotero.org%5C%2Fmarko.vendelin%22%2C%22type%22%3A%22text%5C%2Fhtml%22%7D%7D%7D%2C%22creatorSummary%22%3A%22Laasmaa%20et%20al.%22%2C%22parsedDate%22%3A%222021-02-01%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELaasmaa%2C%20M.%2C%20Branovets%2C%20J.%2C%20Barsunova%2C%20K.%2C%20Karro%2C%20N.%2C%20Lygate%2C%20C.%20A.%2C%20Birkedal%2C%20R.%2C%20%26amp%3B%20Vendelin%2C%20M.%20%282021%29.%20Altered%20calcium%20handling%20in%20cardiomyocytes%20from%20arginine-glycine%20amidinotransferase-knockout%20mice%20is%20rescued%20by%20creatine.%20%3Ci%3EAmerican%20Journal%20of%20Physiology-Heart%20and%20Circulatory%20Physiology%3C%5C%2Fi%3E%2C%20%3Ci%3E320%3C%5C%2Fi%3E%282%29%2C%20H805%26%23x2013%3BH825.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1152%5C%2Fajpheart.00300.2020%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1152%5C%2Fajpheart.00300.2020%3C%5C%2Fa%3E%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Altered%20calcium%20handling%20in%20cardiomyocytes%20from%20arginine-glycine%20amidinotransferase-knockout%20mice%20is%20rescued%20by%20creatine%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Martin%22%2C%22lastName%22%3A%22Laasmaa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jelena%22%2C%22lastName%22%3A%22Branovets%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Karina%22%2C%22lastName%22%3A%22Barsunova%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Niina%22%2C%22lastName%22%3A%22Karro%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Craig%20A.%22%2C%22lastName%22%3A%22Lygate%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rikke%22%2C%22lastName%22%3A%22Birkedal%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marko%22%2C%22lastName%22%3A%22Vendelin%22%7D%5D%2C%22abstractNote%22%3A%22The%20creatine%20kinase%20system%20facilitates%20energy%20transfer%20between%20mitochondria%20and%20the%20major%20ATPases%20in%20the%20heart.%20Creatine-deficient%20mice%2C%20which%20lack%20arginine-glycine%20amidinotransferase%20%28AGAT%29%20to%20synthesize%20creatine%20and%20homoarginine%2C%20exhibit%20reduced%20cardiac%20contractility.%20We%20studied%20how%20the%20absence%20of%20a%20functional%20CK%20system%20influences%20calcium%20handling%20in%20isolated%20cardiomyocytes%20from%20AGAT-knockouts%20and%20wild-type%20littermates%20as%20well%20as%20in%20AGAT-knockout%20mice%20receiving%20lifelong%20creatine%20supplementation%20via%20the%20food.%20Using%20a%20combination%20of%20whole%20cell%20patch%20clamp%20and%20fluorescence%20microscopy%2C%20we%20demonstrate%20that%20the%20L-type%20calcium%20channel%20%28LTCC%29%20current%20amplitude%20and%20voltage%20range%20of%20activation%20were%20significantly%20lower%20in%20AGAT-knockout%20compared%20with%20wild-type%20littermates.%20Additionally%2C%20the%20inactivation%20of%20LTCC%20and%20the%20calcium%20transient%20decay%20were%20significantly%20slower.%20According%20to%20our%20modeling%20results%2C%20these%20changes%20can%20be%20reproduced%20by%20reducing%20three%20parameters%20in%20knockout%20mice%20when%20compared%20with%20wild-type%3A%20LTCC%20conductance%2C%20the%20exchange%20constant%20of%20Ca2%2B%20transfer%20between%20subspace%20and%20cytosol%2C%20and%20SERCA%20activity.%20Because%20tissue%20expression%20of%20LTCC%20and%20SERCA%20protein%20were%20not%20significantly%20different%20between%20genotypes%2C%20this%20suggests%20the%20involvement%20of%20posttranslational%20regulatory%20mechanisms%20or%20structural%20reorganization.%20The%20AGAT-knockout%20phenotype%20of%20calcium%20handling%20was%20fully%20reversed%20by%20dietary%20creatine%20supplementation%20throughout%20life.%20Our%20results%20indicate%20reduced%20calcium%20cycling%20in%20cardiomyocytes%20from%20AGAT-knockouts%20and%20suggest%20that%20the%20creatine%20kinase%20system%20is%20important%20for%20the%20development%20of%20calcium%20handling%20in%20the%20heart.NEW%20%26%20NOTEWORTHY%20Creatine-deficient%20mice%20lacking%20arginine-glycine%20amidinotransferase%20exhibit%20compromised%20cardiac%20function.%20Here%2C%20we%20show%20that%20this%20is%20at%20least%20partially%20due%20to%20an%20overall%20slowing%20of%20calcium%20dynamics.%20Calcium%20influx%20into%20the%20cytosol%20via%20the%20L-type%20calcium%20current%20%28LTCC%29%20is%20diminished%2C%20and%20the%20rate%20of%20the%20sarcoendoplasmic%20reticulum%20calcium%20ATPase%20%28SERCA%29%20pumping%20calcium%20back%20into%20the%20sarcoplasmic%20reticulum%20is%20slower.%20The%20expression%20of%20LTCC%20and%20SERCA%20did%20not%20change%2C%20suggesting%20that%20the%20changes%20are%20regulatory.%22%2C%22date%22%3A%22February%201%2C%202021%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1152%5C%2Fajpheart.00300.2020%22%2C%22ISSN%22%3A%220363-6135%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fjournals.physiology.org%5C%2Fdoi%5C%2Ffull%5C%2F10.1152%5C%2Fajpheart.00300.2020%22%2C%22collections%22%3A%5B%22RTHH5FGZ%22%2C%22BJ28HM24%22%5D%2C%22dateModified%22%3A%222023-05-08T11%3A04%3A12Z%22%7D%7D%5D%7D
Risti, R., Gunn, K. H., Hiis-Hommuk, K., Seeba, N.-N., Karimi, H., Villo, L., Vendelin, M., Neher, S. B., & Lõokene, A. (2023). Combined action of albumin and heparin regulates lipoprotein lipase oligomerization, stability, and ligand interactions. PLOS ONE, 18(4), e0283358. https://doi.org/10.1371/journal.pone.0283358
Laasmaa, M., Branovets, J., Stolova, J., Shen, X., Rätsepso, T., Balodis, M. J., Grahv, C., Hendrikson, E., Louch, W. E., Birkedal, R., & Vendelin, M. (2023). Cardiomyocytes from female compared to male mice have larger ryanodine receptor clusters and higher calcium spark frequency. The Journal of Physiology, 601(18), 4033–4052. https://doi.org/10.1113/JP284515
Birkedal, R., Laasmaa, M., Branovets, J., & Vendelin, M. (2022). Ontogeny of cardiomyocytes: ultrastructure optimization to meet the demand for tight communication in excitation–contraction coupling and energy transfer. Philosophical Transactions of the Royal Society B: Biological Sciences, 377(1864), 20210321. https://doi.org/10.1098/rstb.2021.0321
Branovets, J., Karro, N., Barsunova, K., Laasmaa, M., Lygate, C. A., Vendelin, M., & Birkedal, R. (2021). Cardiac expression and location of hexokinase changes in a mouse model of pure creatine deficiency. American Journal of Physiology-Heart and Circulatory Physiology, 320(2), H613–H629. https://doi.org/10.1152/ajpheart.00188.2020
Laasmaa, M., Branovets, J., Barsunova, K., Karro, N., Lygate, C. A., Birkedal, R., & Vendelin, M. (2021). Altered calcium handling in cardiomyocytes from arginine-glycine amidinotransferase-knockout mice is rescued by creatine. American Journal of Physiology-Heart and Circulatory Physiology, 320(2), H805–H825. https://doi.org/10.1152/ajpheart.00300.2020
All publications: click here
Online supplements and corrections to papers: click here