Atorvastatin attenuates cardiomyocyte loss in adult rats from protein-restricted dams

被引:19
作者
Bezerra, Daniele Goncalves [1 ]
Lacerda Andrade, Livia Marinho [1 ]
Pinto Da Cruz, Fernanda Ornellas [1 ]
Mandarim-De-Lacerda, Carlos Alberto [1 ]
机构
[1] Univ Estado Rio De Janeiro, Inst Biol, Biomed Ctr, Lab Morphometry & Cariovasc Morphol, BR-20551030 Rio De Janeiro, RJ, Brazil
关键词
cardiac remodeling; statins; heart failure prevention; metabolic programming; stereology;
D O I
10.1016/j.cardfail.2007.10.015
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
Background: Statins are cholesterol-lowering drugs that have been proved to prevent cardiac events. Their direct effects on cardiac remodeling, when administered in programmed protein restricted animals, still are unknown. Methods and Results: Wistar male 6-month-old offspring from darns fed normal protein (NP, 19% of protein) or low-protein (LP, 5% of protein) during pregnancy and first 10 days after birth were studied. After weaning, male pups were allocated to untreated or treated groups with atorvastatin (low and high doses, 5 or 30 mg - ka - day) in two different periods (from 21 days old to 3 months old and from 3 to 6 months old). The blood pressure (BP) was 30% greater in untreated LP offspring than in treated offspring (from 165 - 6 mm Hg to 127 +/- 3 mm Hg, P <.01). After 1 month of treatment, only untreated LP offspring continued with high BP. Compared with untreated LP offspring, atorvastatin reduced blood glucose (less 30%, P <.05) and cardiomyocyte size (less 24%, P <.05), whereas untreated LP offspring had greater interstitial fibrosis (plus 74%, P <.01), reduction of myocardial vascularization (less 25%, P <.01) and major reduction of cardiomyocyte number (less 38%, P <.01) than treated LP offspring. Conclusion: Atorvastatin from 3 to 6 months olds in both low and high doses (but not from 0 to 3 months) has beneficial effects improving myocardial vascularization by diminishing fibrosis and cardiomyocyte loss.
引用
收藏
页码:151 / 160
页数:10
相关论文
共 86 条
[1]
Spontaneously hypertensive rats left ventricular cardiomyocyte loss attenuation through different edible oils long-term intake [J].
Aguila, MB ;
Pinheiro, AR ;
Mandarim-de-Lacerda, CA .
INTERNATIONAL JOURNAL OF CARDIOLOGY, 2005, 100 (03) :461-466
[2]
Blood pressure, ventricular volume and number of cardiomyocyte nuclei in rats fed for 12 months on diets differing in fat composition [J].
Aguila, MB ;
Mandarim-de-Lacerda, CA .
MECHANISMS OF AGEING AND DEVELOPMENT, 2001, 122 (01) :77-88
[3]
Overweight is gender-dependent in prenatal protein-calorie restricted adult rats acting on the blood pressure and the adverse cardiac remodeling [J].
Almeida, JR ;
Mandarim-De-Lacerda, CA .
LIFE SCIENCES, 2005, 77 (12) :1307-1318
[4]
[Anonymous], 1979, STEREOLOGICAL METHOD
[5]
Myocardial aging - A stem cell problem [J].
Anversa, P ;
Rota, M ;
Urbanek, K ;
Hosoda, T ;
Sonnenblick, EH ;
Leri, A ;
Kajstura, J ;
Bolli, R .
BASIC RESEARCH IN CARDIOLOGY, 2005, 100 (06) :482-493
[6]
Myocyte renewal and ventricular remodelling [J].
Anversa, P ;
Nadal-Ginard, B .
NATURE, 2002, 415 (6868) :240-243
[7]
Ventricular myocytes are not terminally differentiated in the adult mammalian heart [J].
Anversa, P ;
Kajstura, J .
CIRCULATION RESEARCH, 1998, 83 (01) :1-14
[8]
MORPHOMETRIC STUDY OF EARLY POSTNATAL-DEVELOPMENT IN THE LEFT AND RIGHT VENTRICULAR MYOCARDIUM OF THE RAT .1. HYPERTROPHY, HYPERPLASIA, AND BINUCLEATION OF MYOCYTES [J].
ANVERSA, P ;
OLIVETTI, G ;
LOUD, AV .
CIRCULATION RESEARCH, 1980, 46 (04) :495-502
[9]
Atorvastatin-induced cardioprotection is mediated by increasing inducible nitric oxide synthase and consequent S-nitrosylation of cyclooxygenase-2 [J].
Atar, S ;
Ye, YM ;
Lin, Y ;
Freeberg, SY ;
Nishi, SP ;
Rosanio, S ;
Huang, MH ;
Uretsky, BF ;
Perez-Polo, JR ;
Birnbaum, Y .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2006, 290 (05) :H1960-H1968
[10]
Austin A, 1995, J ANAT, V187, P641