Evidence map›Paper›PMID 22181043›Full record

ReviewArchives of physiology and biochemistry2012

Mitochondrial mitophagic mechanisms of myocardial matrix metabolism and remodelling.

Thomas P Vacek, Jonathan C Vacek, Suresh C Tyagi

Abstract readReview
In one paragraph

Review in Archives of physiology and biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Mitochondrial Adaptation to Mechanical Stress in Cardiac Ageing and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  3. Homocysteinylation of Fibrinogen: A Post-Translational Link to Thrombosis.International journal of molecular sciences · 2025
    Review
  4. Review
  5. Article
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  7. Review
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  13. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Thomas P VacekDepartment of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, KY 40202, USA.
Jonathan C Vacek
Suresh C Tyagi
University of Louisville · US

Funding

Reversing diabetic muscle myopathy by exercise and exosomesR01HL074185 · NHLBI · UNIVERSITY OF LOUISVILLE · PI TYAGI, SURESH C. · 2003 to 2018
$5.7M
Mechanism of Vascular Remodeling in HyperhomocysteinemiaR01HL071010 · NHLBI · UNIVERSITY OF MISSISSIPPI MEDICAL CENTER · PI TYAGI, SURESH C. · 2002 to 2010
$2.7M
Mitophagic and anti-angiogenic mechanism of heart failureR01HL108621 · NHLBI · UNIVERSITY OF LOUISVILLE · PI TYAGI, SURESH C. · 2011 to 2015
$1.8M
Mechanisms of Cerebral Vascular RemodelingR01NS051568 · NINDS · UNIVERSITY OF LOUISVILLE · PI TYAGI, SURESH C. · 2007 to 2011
$1.6M
Implications of Endothelial-Myocyte Uncoupling in Cardiac ArrhythmiaR01HL088012 · NHLBI · UNIVERSITY OF LOUISVILLE · PI TYAGI, SURESH C. · 2007 to 2010
$1.5M
NHLBI NIH HHS HL108621NHLBI NIH HHS HL-71010NHLBI NIH HHS HL-74185NHLBI NIH HHS HL-88012NHLBI NIH HHS R01 HL071010NHLBI NIH HHS R01 HL074185NHLBI NIH HHS R01 HL088012NHLBI NIH HHS R01 HL108621NINDS NIH HHS NS-51568NINDS NIH HHS R01 NS051568
6 · The paper itself

Abstract

High levels of homocysteine (Hcy), known as hyperhomocysteinmia (HHcy), are correlated with an increase in extracellular matrix remodelling (ECM) via the matrix metalloproteinases (MMPs) and plasminogen/plasmin system. This results in an increase deposition of collagen that leads to endothelial-myocyte (EM) and myocyte-myocyte (MM) uncoupling; the physiological consequences are a plethora of cardiovascular pathologies. Homocysteine-induced increase in intracellular and mitochondrial Ca(2+) plays an important role in increasing reactive oxygen species (ROS) within mitochondria and instigating mitophagy within the cell. This occurs via several Hcy-mitigated processes: agonizing N-methyl-d-aspartate receptor-1 (NMDA-R1), decreasing expression of peroxisome proliferator activator receptor (PPAR) [thereby increasing oxidation], impairing Ca(2+) handling via Na(+)/Ca(2+) exchanger (NCX1) and Sarco endoplasmic reticulum Ca(2+) ATPase (SERCA-2a). The end result is an increase in ROS that directly or indirectly lead to MMP activation within mitochondria or the cytoplasm. Hcy induces a mitochondrial permeability transition that allows MMPs to be released from mitochondria thereby metabolizing matrix and impairing cardiac function. Further work remains to be elucidated concerning the specific mitochondrial mitophagic mechanisms under which matrix metabolism and remodelling occurs. Moreover, the therapeutic implications of NMDA and PPAR ligands are some promise to patient.

Indexed as

AnimalsAutophagyCalciumExtracellular MatrixFibrinolysinHomocysteineHumansHyperhomocysteinemiaMatrix MetalloproteinasesMiceMitochondria, HeartMyocardiumMyocytes, CardiacOxidative StressPermeabilityPeroxisome Proliferator-Activated ReceptorsCalciumFibrinolysinHomocysteineMatrix MetalloproteinasesPeroxisome Proliferator-Activated ReceptorsPlasminogenReactive Oxygen SpeciesReceptors, N-Methyl-D-AspartateSarcoplasmic Reticulum Calcium-Transporting ATPasesSodium-Calcium Exchangersodium-calcium exchanger 1

Identifiers

PMID22181043
PMCPMC3269507
OpenAlexW2014477929

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.