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Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment.
Circulation. 2004 Jun 01; 109(21):2572-80.Circ

Abstract

BACKGROUND

We investigated whether the improvement of cardiac function and remodeling after myocardial infarction (MI) by granulocyte colony-stimulating factor (G-CSF) relates to acceleration of the healing process, in addition to myocardial regeneration.

METHODS AND RESULTS

In a 30-minute coronary occlusion and reperfusion rabbit model, saline (S) or 10 microg x kg(-1) x d(-1) of human recombinant G-CSF (G) was injected subcutaneously from 1 to 5 days after MI. Smaller left ventricular (LV) dimension, increased LV ejection fraction, and thicker infarct-LV wall were seen in G at 3 months after MI. At 2, 7, and 14 days and 3 months after MI, necrotic tissue areas were 14.2+/-1.5/13.4+/-1.1, 0.4+/-0.1/1.8+/-0.5*, 0/0, and 0/0 mm2 x slice(-1) x kg(-1), granulation areas 0/0, 4.0+/-0.7/8.5+/-1.0*, 3.9+/-0.8/5.7+/-0.7,* and 0/0 mm2 x slice(-1) x kg(-1), and scar areas 0/0, 0/0, 0/0, and 4.2+/-0.5/7.9+/-0.9* mm2 x slice(-1) x kg(-1) in G and S, respectively (*P<0.05, G versus S). Clear increases of macrophages and of matrix metalloproteinases (MMP) 1 and 9 were seen in G at 7 days after MI. This suggests that G accelerates absorption of necrotic tissues via increase of macrophages and reduces granulation and scar tissues via expression of MMPs. Meanwhile, surviving myocardial tissue areas within the risk areas were significantly increased in G despite there being no difference in LV weight, LV wall area, or cardiomyocyte size between G and S. Confocal microscopy revealed significant increases of cardiomyocytes with positive 3,3,3',3'-tetramethylindocarbocyanine perchlorate and positive troponin I in G, suggesting enhanced myocardial regeneration by G.

CONCLUSIONS

The acceleration of the healing process and myocardial regeneration may play an important role for the beneficial effect of post-MI G-CSF treatment.

Authors+Show Affiliations

Second Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa Machi, Gifu, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15123535

Citation

Minatoguchi, Shinya, et al. "Acceleration of the Healing Process and Myocardial Regeneration May Be Important as a Mechanism of Improvement of Cardiac Function and Remodeling By Postinfarction Granulocyte Colony-stimulating Factor Treatment." Circulation, vol. 109, no. 21, 2004, pp. 2572-80.
Minatoguchi S, Takemura G, Chen XH, et al. Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment. Circulation. 2004;109(21):2572-80.
Minatoguchi, S., Takemura, G., Chen, X. H., Wang, N., Uno, Y., Koda, M., Arai, M., Misao, Y., Lu, C., Suzuki, K., Goto, K., Komada, A., Takahashi, T., Kosai, K., Fujiwara, T., & Fujiwara, H. (2004). Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment. Circulation, 109(21), 2572-80.
Minatoguchi S, et al. Acceleration of the Healing Process and Myocardial Regeneration May Be Important as a Mechanism of Improvement of Cardiac Function and Remodeling By Postinfarction Granulocyte Colony-stimulating Factor Treatment. Circulation. 2004 Jun 1;109(21):2572-80. PubMed PMID: 15123535.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment. AU - Minatoguchi,Shinya, AU - Takemura,Genzou, AU - Chen,Xue-Hai, AU - Wang,Ningyuan, AU - Uno,Yoshihiro, AU - Koda,Masahiko, AU - Arai,Masazumi, AU - Misao,Yu, AU - Lu,Chuanjiang, AU - Suzuki,Koji, AU - Goto,Kazuko, AU - Komada,Ai, AU - Takahashi,Tomoyuki, AU - Kosai,Kenichiro, AU - Fujiwara,Takako, AU - Fujiwara,Hisayoshi, Y1 - 2004/05/03/ PY - 2004/5/5/pubmed PY - 2004/12/16/medline PY - 2004/5/5/entrez SP - 2572 EP - 80 JF - Circulation JO - Circulation VL - 109 IS - 21 N2 - BACKGROUND: We investigated whether the improvement of cardiac function and remodeling after myocardial infarction (MI) by granulocyte colony-stimulating factor (G-CSF) relates to acceleration of the healing process, in addition to myocardial regeneration. METHODS AND RESULTS: In a 30-minute coronary occlusion and reperfusion rabbit model, saline (S) or 10 microg x kg(-1) x d(-1) of human recombinant G-CSF (G) was injected subcutaneously from 1 to 5 days after MI. Smaller left ventricular (LV) dimension, increased LV ejection fraction, and thicker infarct-LV wall were seen in G at 3 months after MI. At 2, 7, and 14 days and 3 months after MI, necrotic tissue areas were 14.2+/-1.5/13.4+/-1.1, 0.4+/-0.1/1.8+/-0.5*, 0/0, and 0/0 mm2 x slice(-1) x kg(-1), granulation areas 0/0, 4.0+/-0.7/8.5+/-1.0*, 3.9+/-0.8/5.7+/-0.7,* and 0/0 mm2 x slice(-1) x kg(-1), and scar areas 0/0, 0/0, 0/0, and 4.2+/-0.5/7.9+/-0.9* mm2 x slice(-1) x kg(-1) in G and S, respectively (*P<0.05, G versus S). Clear increases of macrophages and of matrix metalloproteinases (MMP) 1 and 9 were seen in G at 7 days after MI. This suggests that G accelerates absorption of necrotic tissues via increase of macrophages and reduces granulation and scar tissues via expression of MMPs. Meanwhile, surviving myocardial tissue areas within the risk areas were significantly increased in G despite there being no difference in LV weight, LV wall area, or cardiomyocyte size between G and S. Confocal microscopy revealed significant increases of cardiomyocytes with positive 3,3,3',3'-tetramethylindocarbocyanine perchlorate and positive troponin I in G, suggesting enhanced myocardial regeneration by G. CONCLUSIONS: The acceleration of the healing process and myocardial regeneration may play an important role for the beneficial effect of post-MI G-CSF treatment. SN - 1524-4539 UR - https://www.unboundmedicine.com/medline/citation/15123535/Acceleration_of_the_healing_process_and_myocardial_regeneration_may_be_important_as_a_mechanism_of_improvement_of_cardiac_function_and_remodeling_by_postinfarction_granulocyte_colony_stimulating_factor_treatment_ L2 - https://www.ahajournals.org/doi/10.1161/01.CIR.0000129770.93985.3E?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -