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Abstract <p>Hypertrophic changes in the ventricular myocardium accompanymost cardiovascular diseases and represent a serious risk factorfor sudden cardiac death. To date, a wide range of in vitro andin vivo models of hypertrophy have been developed; however, noneof them allow for the simultaneous investigation of both biochemicaland physiological aspects of its pathogenesis. This study proposesa method based on the induction of left ventricular hypertrophy(LVH) resulting from renovascular hypertension in rats, followedby the isolation of cardiomyocytes from their hearts. The studyincluded 68 animals (32 1K1C type rats, 16 1K type rats, and 20sham-operated (SO) rats). To induce LVH in the “one kidney one clip”(1K1C) rats, a clip was placed on the renal artery of the left kidneyto restrict blood flow, after which the right kidney was removed.In the “one kidney” (1K) group, the right kidney was removed whilethe left kidney was remained intact, whereas in SO rats, the abdominalcavity was opened and then sutured without any manipulation of thekidneys. The latter two groups served as controls. After 1.5 months,the left ventricular mass in 1K1C rats exceeded that in both controlgroups by 1.2 times, while the arterial pressure in the 1K1C groupincreased by 1.4 times compared to both controls. Additionally,1K1C rats exhibited a 1.4-fold increase in serum and urinary ureaconcentrations and a 1.5-fold enhancement in renal excretion, asassessed by creatinine clearance, compared to the control groups.The serum concentration of B-type natriuretic peptide (BNP) in 1K1Crats was twice as high as in the control groups. After LVH induction,primary cardiomyocyte cultures were derived from the hearts of controland hypertrophic rats. In the conditioned medium of the primaryculture of ventricular cardiomyocytes from 1K1C rats, the BNP concentrationwas 3.4 times higher than in the control groups. Thus, it was demonstratedthat cardiomyocytes isolated from 1K1C rats retain a hypertrophicphenotype, and this combined approach can be used to study cardiachypertrophy in vivo and in vitro.</p>

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A Combination of in vitro and in vivo Approaches to Studying the Mechanisms of Myocardial Hypertrophy Development in Adult Rats with Renovascular Hypertension

  • 期刊论文

  • 发表日期：

    2025年7月1日

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  • A. V. Makeeva,
  • M. M. Artemieva,
  • D. A. Adasheva,
  • V. E. Shein,
  • N. A. Medvedeva,
  • D. V. Serebryanaya

摘要

Abstract

Hypertrophic changes in the ventricular myocardium accompanymost cardiovascular diseases and represent a serious risk factorfor sudden cardiac death. To date, a wide range of in vitro andin vivo models of hypertrophy have been developed; however, noneof them allow for the simultaneous investigation of both biochemicaland physiological aspects of its pathogenesis. This study proposesa method based on the induction of left ventricular hypertrophy(LVH) resulting from renovascular hypertension in rats, followedby the isolation of cardiomyocytes from their hearts. The studyincluded 68 animals (32 1K1C type rats, 16 1K type rats, and 20sham-operated (SO) rats). To induce LVH in the “one kidney one clip”(1K1C) rats, a clip was placed on the renal artery of the left kidneyto restrict blood flow, after which the right kidney was removed.In the “one kidney” (1K) group, the right kidney was removed whilethe left kidney was remained intact, whereas in SO rats, the abdominalcavity was opened and then sutured without any manipulation of thekidneys. The latter two groups served as controls. After 1.5 months,the left ventricular mass in 1K1C rats exceeded that in both controlgroups by 1.2 times, while the arterial pressure in the 1K1C groupincreased by 1.4 times compared to both controls. Additionally,1K1C rats exhibited a 1.4-fold increase in serum and urinary ureaconcentrations and a 1.5-fold enhancement in renal excretion, asassessed by creatinine clearance, compared to the control groups.The serum concentration of B-type natriuretic peptide (BNP) in 1K1Crats was twice as high as in the control groups. After LVH induction,primary cardiomyocyte cultures were derived from the hearts of controland hypertrophic rats. In the conditioned medium of the primaryculture of ventricular cardiomyocytes from 1K1C rats, the BNP concentrationwas 3.4 times higher than in the control groups. Thus, it was demonstratedthat cardiomyocytes isolated from 1K1C rats retain a hypertrophicphenotype, and this combined approach can be used to study cardiachypertrophy in vivo and in vitro.