Pregnancy-induced physiological hypertrophy protects against cardiac ischemia-reperfusion injury

Abstract

Objective: Cardiac hypertrophy is a compensatory response of the heart to maintain its pumping capacity. Cardiac hypertrophy can be divided into pathological hypertrophy and physiological hypertrophy. The major forms of physiological hypertrophy include developing in response to developmental maturation, exercise, and pregnancy, which is adaptive and beneficial. Exercise has well-known beneficial cardiovascular effects and has recently been shown to be protective for myocardial ischemia-reperfusion injury. However, there are conflicting reports for the cardiac protective effects of pregnancy-induced hypertrophy. In the present study, we investigated the effects of pregnancy-induced physiological hypertrophy in cardiac ischemia-reperfusion injury and if cardiac progenitor cells were activated during pregnancy.

Methods: Physiological hypertrophy was induced in pregnancy and the mRNA levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were determined by real-time polymerase chain reactions (RT-PCRs) analysis. Triphenyltetrazolium chloride staining was used to determine the cardiac ischemia-reperfusion injury. c-Kit and Nkx2.5 levels were determined by RT-PCRs, western blot and immunofluorescent staining.

Results: Heart weight (HW) and the ratio of HW to tibia length were increased while mRNA levels of ANP and BNP remained unchanged. Pregnancy-induced physiological hypertrophy protected against cardiac ischemia-reperfusion injury. In pregnancy, c-Kit positive cardiac progenitor cells were activated.

Conclusion: This study presents that pregnancy-induced physiological hypertrophy activates cardiac progenitor cells and thereafter protects against cardiac ischemia-reperfusion injury.

Keywords: Pregnancy; cardiac progenitor cells; hypertrophy; ischemia/reperfusion; physiological.

Figure 1

Physiological hypertrophy is induced in pregnancy. A: Heart weight; B: Body weight; C: Heart weight/Tibia length; D: Heart weight/Body weight; E: ANP mRNA level; F: BNP mRNA level. *, compared to the non-pregnancy group, P less than 0.05.

Figure 2

Pregnancy-induced physiological hypertrophy protects against cardiac ischemia-reperfusion injury. A: Representative sections of NP and LP hearts in cardiac ischemia-reperfusion injury; B: Infarct size is reduced in LP mice. *, compared to the non-pregnancy group, P less than 0.05. NP (n=5), nonpregnant diestrus stage; LP (n=6), late pregnant.

Figure 3

Pregnancy upregulates the expression of c-Kit. A: Nkx2.5 mRNA level; B: c-Kit mRNA level; C: Representative blots of c-Kit in non-pregnancy and pregnancy group; D: c-Kit protein level. *, compared to the non-pregnancy group, P less than 0.05. n=3 per group.

Figure 4

Pregnancy activates c-Kit positive cardiac progenitor cells. Representative pictures of c-Kit in non-pregnancy (A) and pregnancy group (B). Pregnancy activates c-Kit positive cardiac progenitor cells (C). *, compared to the non-pregnancy group, P less than 0.05. n=4 per group.