CoChat
Sign Up
Cited by 116Cardiac Fibrosis and RemodelingCardiac Ischemia and ReperfusionCongenital heart defects research

Inhibition of Granulation Tissue Cell Apoptosis During the Subacute Stage of Myocardial Infarction Improves Cardiac Remodeling and Dysfunction at the Chronic Stage

Hayakawa, Kenji, Takemura, Genzou, Kanoh, Motoo, Li, Yiwen, Koda, Masahiko, Kawase, Yukinori, Maruyama, Rumi, Okada, Hideshi +3 more·2003·Circulation
DOI 10.1161/01.cir.0000074225.62168.68
Open this paper in CoChat — free account

Abstract

Background— Granulation tissue cells at the subacute stage of myocardial infarction (MI) are eliminated by apoptosis to finally make a scar at the chronic stage. We hypothesized that postinfarct inhibition of apoptosis might preserve myofibroblasts and endothelial cells in granulation and modulate chronic left ventricular (LV) remodeling and heart failure. Methods and Results— A pancaspase inhibitor, Boc-Asp-fmk (BAF, 10 μmol/kg per day), or vehicle (control) was given to rats with experimental large MI. The treatment was started on the third day after MI and continued until 4-week-old MI. Two weeks later, the apoptosis of granulation tissue cells was significantly reduced and conversely, the cell population was greater in BAF. Twelve weeks later, BAF showed significantly greater survival rates (84% versus 42%) with significantly smaller LV cavity, lower LV end-diastolic pressure and central venous pressure, and higher LV dP/dt, which indicated improvement of LV remodeling and dysfunction. A scar was established in old infarct of control subjects, but in BAF, the infarct wall was thicker because of greater old infarct area, which contained abundant myofibroblasts and vessels. Surprisingly, many of the α-smooth muscle actin–positive myofibroblast-like cells in BAF, making bundles and running parallel to the survived cardiomyocytes, were ultrastructurally mature smooth muscle cells with contractile phenotype. Cardiomyocyte apoptosis in the infarct area was equally rare in each group. Conclusions— The postinfarct treatment with BAF improved LV remodeling and dysfunction through inhibition of granulation tissue cell apoptosis. These findings imply a new therapeutic strategy against postinfarct heart failure.

Integrity signals

Registry

Crossref · 10.1161/01.cir.0000074225.62168.68

Cites

22 of 22 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Inhibiting caspases can both reduce the occurrence of heart failure or slow its progression after MI as well as improve contractile function.

    “Accordingly, inhibiting caspases can both reduce the occurrence of heart failure or slow its progression after MI (45, 131, 374, 383, 384) as well as improve contractile function (45).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [131]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Hayakawa, K., Takemura, G., Kanoh, M., Li, Y., Koda, M., Kawase, Y., Maruyama, R., Okada, H., Minatoguchi, S., Fujiwara, T., & Fujiwara, H.
Affiliations
Kyoto Women's University (JP)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2003-07-08
Volume
108
Issue
1
Pages
104-109
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.0000074225.62168.68
OpenAlex
W2158635027
Cited by
116
References
22
Citations by year
2026: 3 · 2025: 2 · 2024: 7 · 2023: 2 · 2022: 7 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 9 · 2012: 4
FWCI
5.41
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Keywords
myocardial infarction, apoptosis inhibition, granulation tissue, cardiac remodeling, left ventricular dysfunction, myofibroblasts, endothelial cells, cardiomyocyte apoptosis, alpha-smooth muscle actin, scar formation
MeSH terms
Amino Acid Chloromethyl Ketones, Animals, Chronic Disease, Disease Models, Animal, Granulation Tissue, Heart, Male, Myocardial Infarction, Myocardium, Cysteine Proteinase Inhibitors, Survival Rate, Rats, Wistar, Apoptosis, Disease Progression, Ventricular Dysfunction, Ventricular Remodeling, Rats, Caspase Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review