Myocardial DNA synthesis in experimental cardiac hypertrophy

Morkin, Eugene; Ashford, Thomas P.

doi:10.1152/ajplegacy.1968.215.6.1409

Cited by 199 publications

(73 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a method for measuring nuclear and cellular multiplication, nuclear count morphometry is uniquely different from autoradiographic DNA-labeling techniques. Whereas the latter can be used to show nuclear DNA synthesis at specific times (Morkin and Ashford, 1968;Grove et al, 1969;Hollenberg et al, 1977;Dowell and McManus, 1978), the morphometric approach yields a numerical evaluation of changes in the absolute numbers of nuclei and cells during a specified time interval (Anversa et al, 1978(Anversa et al, , 1979Loud et al, 1978). Morphometry alone cannot distinguish among the several mechanisms by which binucleate myocytes may be formed: binucleate cell division, nuclear division without cell division in a mononucleate cell, or fusion or mononucleate cells.…”

Section: Discussionmentioning

confidence: 99%

Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. I. Hypertrophy, hyperplasia, and binucleation of myocytes.

Anversa¹,

Olivetti²,

Loud³

1980

Circulation Research

185

View full text Add to dashboard Cite

SUMMARY We reviewed the absolute amd differential growths of the myocyte populations in the left (L) and right (R) ventricular myocardium morphometrically from 1 to 5 days and from 5 to 11 days after birth. From 1 to 11 days hypertrophy of the average myocyte in the ventricles was (L) 2.7-and (R) 2.4-fold, and myocyte proliferation was (L) 2.0-and (R) 1.2-fold. Mean cell volume, cell length, and percent binucleation of cardiac myocytes were similar in both ventricles at 1, 5, and 11 days of age. During this period, average myocyte length increased 2-fold (12 sarcomere lengths), and the percentage of binucleate myocytes increased approximately from 2.7 to 17 to 48%. Myocyte hypertrophy from 1 to 5 days resulted mainly from an increase in the volume of cytoplasm per nucleus and from 5 to 11 days from the accumulation of binucleate cells. No differences were observed in the characteristics of epicardial and endocardial myocytes in either ventricle up to 11 days of age. The 61% greater proliferation of myocytes in the left ventricle was the principal basis for the development of a 2-fold difference in ventricular weight gains: (L) 6.2-and (R) 3.4-fold. No increase in right ventricular midwall thickness was observed, in contrast to a 2.7-fold increase of the left ventricle. It was concluded that, as a result of the circulatory changes occurring shortly after birth, right ventricular growth is analogous to eccentric hypertrophy, whereas left ventricular growth represents a combination of eccentric and concentric hypertrophy. Circ Res 46: 495-502, 1980 GROWTH of the myocardium during the early postnatal period must accommodate not only the increasing demands of the rapidly growing animal but also the relatively abrupt changes in the patterns of blood flow and circulatory resistance occuring shortly after birth. Work required of the left and right ventricles is approximately equal as they pump in parallel during fetal life (Heymann and Rudolph, 1973;Rudolph, 1974). With closure of the foramen ovale and ductus arteriosus after birth, blood flow is henceforth in series through the right and left ventricles, resulting in a greater volume work load on each ventricle. In the same period, pulmonary resistance is lowered by expansion of the collapsed lungs (Klopfenstein and Rudolph, 1978;Rudolph, 1979), peripheral resistance increases with loss of the placental circulation (Rudolph, 1970), and the pressure load on the left ventricle becomes significantly greater than that on the right ventricle (Assali et al., 1965). The combi-

show abstract

Section: Discussionmentioning

confidence: 99%

Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. I. Hypertrophy, hyperplasia, and binucleation of myocytes.

Anversa¹,

Olivetti²,

Loud³

1980

Circulation Research

185

View full text Add to dashboard Cite

show abstract

“…Cardiac fibroblasts also play an integral role in cardiac remodeling. Although the cardiomyocytes hypertrophy, the fibroblasts proliferate and increase their production of extracellular matrix (17,18). These events increase the volume of fibroblasts and matrix relative to that of myocytes in the hypertrophied heart compared with normal heart, which ultimately results in ventricular dysfunction and heart failure (19).…”

Section: Introductionmentioning

confidence: 99%

Osteopontin is produced by rat cardiac fibroblasts and mediates A(II)-induced DNA synthesis and collagen gel contraction.

Ashizawa¹,

Graf²,

Yung³

et al. 1996

J. Clin. Invest.

227

166

View full text Add to dashboard Cite

Angiotensin II (A II ) is a critical factor in cardiac remodeling which involves hypertrophy, fibroblast proliferation, and extracellular matrix production. However, little is known about the mechanism by which A II accelerates these responses. Osteopontin is an acidic phosphoprotein with RGD (arginine-glycine-aspartate) sequences that are involved in the vascular smooth muscle cell remodeling process. We identified the presence of osteopontin mRNA and protein in cultured rat cardiac fibroblasts and its prominent regulation by A II (10 Ϫ 11 M). Osteopontin message levels were increased fourfold ( P Ͻ 0.01) and protein fivefold ( P Ͻ 0.05) at 24 h after addition of A II (10 Ϫ 7 M). This response was inhibited by the AT 1 receptor blocker, losartan. Osteopontin mRNA levels were increased in hypertrophied ventricles from animals with renovascular hypertension (1.6-fold, P Ͻ 0.05) and aortic banding (2.9-fold, P Ͻ 0.05). To examine the function of osteopontin, we determined its effects on ( a ) the ability of cardiac fibroblasts to contract three-dimensional collagen gels and ( b ) cardiac fibroblast growth. A monoclonal antibody against osteopontin partially blocked A II -induced three-dimensional collagen gel contraction by cardiac fibroblasts (64 Ϯ 4 vs. 86 Ϯ 5% in the presence of antibody, P Ͻ 0.05), while osteopontin itself promoted contraction of the gels by fibroblasts (71 Ϯ 5%, P Ͻ 0.05 compared with control). Either a monoclonal antibody against ␤ 3 integrin which is a ligand for osteopontin or the RGD peptide blocked both A II and osteopontin-induced collagen gel contraction. Thus, the osteopontin RGD sequence binds to ␤ 3 integrins on the fibroblast to promote fibroblast binding to collagen. A II induced a threefold increase in DNA synthesis of cardiac fibroblasts, which was completely blocked by antibodies against osteopontin and ␤ 3 integrin, or by RGD peptide, but not by controls. Thus, A II -induced growth of cardiac fibroblasts also requires osteopontin engagement of the ␤ 3 integrin. Taken together, these results provide the first evidence that osteopontin is a potentially important mediator of A II regulation of cardiac fibroblast behavior in the cardiac remodeling process. ( J. Clin. Invest. 1996. 98:2218-2227.)

show abstract

“…Experimental model: An abdominal aorta constricted (AC) model of pressure-over loaded heart was created in rats according to the procedures described by Morkin et al [23]. After anesthesia was induced with an intraperitoneal injection of sodium pentobarbital (NEMBUTAL Injection : Dainippon Pharmaceutical Co., Ltd. Japan) a ventral abdominal laparotomy was performed to expose the aorta.…”

Section: Methodsmentioning

confidence: 99%

Effect of Intermittent Administration of Sustained Release Isosorbide Dinitrate (sr-ISDN) in Rats with Pressure-Overload Heart

Shimamura

Endo

Kutsuna

et al. 2006

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

ABSTRACT. Recent studies have demonstrated the benefits of nitric oxide (NO) on myocardial hypertrophy and myocardial fibrosis. It was suggested that NO has a protective effect on myocardial cell through the neurohormonal system. This effect serves to highlight the important role of NO in maintaining the function and form of heart with chronic heart failure. However, there are no known reports about on the effect of prolonged administration of nitrate on pressure over-load heart. This study was conducted to examine the longterm effect of oral nitrate therapy in rats with pressure-overloaded heart. An abdominal aorta constricted (AC) model of pressure-overloaded heart was created in male Wistar rats. Sustained release isosorbide dinitrate (sr-ISDN) (5 mg/kg once a daily) was administered to the rats once a daily for 12 weeks. The animals were euthanized during the study period, and the heart was collected and weighed. Histopathological examination was performed to evaluate the effect of sr-ISDN on myocardial hypertrophy and fibrosis. The ratio of heart to body weight increased significantly in AC rat and this increase was significantly prevented by sr-ISDN treatment. Histopathological examination showed significant increase in fibrotic area of AC rat compared to sham rat, this increase was inhibited by sr-ISDN treatment. Cardiomyocyte transverse diameter was significantly increased in AC rat compared with sham rat, but this increase tended to decrease by sr-ISDN treatment. In conclusion, intermittent administration with sr-ISDN has mild effect in inhibiting cardiac hypertrophy and marked effect in inhibiting fibrosis due to pressure-overload. KEY WORDS: aortic constrict model, cardiac fibrosis, cardiac hypertrophy, isosorbide dinitrate, rat.

show abstract

Myocardial DNA synthesis in experimental cardiac hypertrophy

Cited by 199 publications

References 0 publications

Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. I. Hypertrophy, hyperplasia, and binucleation of myocytes.

Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. I. Hypertrophy, hyperplasia, and binucleation of myocytes.

Osteopontin is produced by rat cardiac fibroblasts and mediates A(II)-induced DNA synthesis and collagen gel contraction.

Effect of Intermittent Administration of Sustained Release Isosorbide Dinitrate (sr-ISDN) in Rats with Pressure-Overload Heart

Contact Info

Product

Resources

About