1992 Fiscal Year Final Research Report Summary
EXPERIMENTAL STUDY ON THE PATHOGENESIS OF APICAL HYPERTROPHY
| Project/Area Number |
02454263
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | KURUME UNIVERSITY |
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Principal Investigator |
KOGA Yoshinori KURUME UNIVERSITY; THE 3RD DEPARTMENT OF MEDICINE; ASSOCIATE PROFESSOR, 医学部, 助教授 (50080669)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMI Gensho KURUME UNIVERSITY; THE 3RD DEPARTMENT OF MEDICINE; MEDICAL ASSISTANT, 医学部, 助手 (90203405)
NAKATA Masashi KURUME UNIVERSITY; THE 3RD DEPARTMENT OF MEDICINE; MEDICAL ASSISTANT, 医学部, 助手 (70180304)
KAJIYAMA Kiminori KURUME UNIVERSITY; THE 3RD DEPARTMENT OF MEDICINE; ASSISTANT PROFESSOR, 医学部, 講師 (00175275)
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| Project Period (FY) |
1990 – 1992
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| Keywords | Apical Hypertrophy / Pressure Overload / Cardiac Hypertrophy / Norepinephrine / Protein Kinase C / Skeletal alpha-actin m-RNA |
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| Research Abstract |
Apical hypertrophy, initially reported from Japan, presents several clinical profiles distinct from classical hypertrophic cardiomyopathy, whereas mechanisms for localization of abnormal hypertrophy to the ventricular apex remains to be investigated. The present study hypothesizes that the apical myocardium manifests a greater hypertrophic response to pressure overload associated with higher activation of protein-kinase C (PKC). In Wistar rats and SHR, myocardial norepinephrine content was lower in the apex, and higher in the left ventricular free wall, consistent with reported distribution of the sympathetic nerve. Pressure overload produced by abdominal aortic constriction (AC) induced increases in myocardial norepinephrine levels in both strains, while its local gradient remained unchanged. Myocardial levels of inositol-triphosphate did not show a local gradient. The PKC activity in the apical myocardium was lower in Wistar, but not different in SHR. AC induced significant increases
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in PKC activity in the apical and septal myocardium of SHR, although these increases were not observed in Wistar. These observations suggested that pressure overload could induce differential activation of PKC in some pathological conditions like SHR.
Pressure overload induces isoformic changes in contractile proteins, including myosin heavy chain and alpha-actin. With the primer extension method, we confirmed re-expression of skeletal alpha-actin (s-ACT) m-RNA after AC in Wistar rats. The re-expression of s-ACT m-RNA at 6 hours after AC was greater in the endocardium than in the epicardium, and also higher in the apical endocardium than in the basal endocardium.
These greater activation of PKC and re-expression of s-ACT m-RNA in the apical myocardium at the early developmental stage of pressure overload hypertrophy might be attributed to decreased sympathetic innervation or higher wall stress imposed by elevated pressure. The apical myocardium could thus manifest an enhanced hypertrophic response to pressure overload, that could be related to the pathogenesis of apical hypertrophy. Less
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