The heart has two major modalities of hypertrophy in response to hemodynamic loads: concentric and eccentric hypertrophy caused by pressure and volume overload (VO), respectively. However, the molecular mechanism of eccentric hypertrophy remains poorly understood. Here we demonstrate that the Akt-mammalian target of rapamycin (mTOR) axis is a pivotal regulator of eccentric hypertrophy during VO. While mTOR in the heart was activated in a left ventricular end-diastolic pressure (LVEDP)-dependent manner, mTOR inhibition suppressed eccentric hypertrophy and induced cardiac atrophy even under VO. Notably, Akt was ubiquitinated and phosphorylated in response to VO, and blocking the recruitment of Akt to the membrane completely abolished mTOR activation. Various growth factors were upregulated during VO, suggesting that these might be involved in Akt-mTOR activation. Furthermore, the rate of eccentric hypertrophy progression was proportional to mTOR activity, which allowed accurate estimation of eccentric hypertrophy by time-integration of mTOR activity. These results suggested that the Akt-mTOR axis plays a pivotal role in eccentric hypertrophy, and mTOR activity quantitatively determines the rate of eccentric hypertrophy progression. As eccentric hypertrophy is an inherent system of the heart for regulating cardiac output and LVEDP, our findings provide a new mechanistic insight into the adaptive mechanism of the heart.

The purpose of this study was

The optimal titration of VNS would maximize benefits for CHF and minimize adverse effects.

In this study, smoking, sedentary work, short sleep time, and the Japanese-style breakfast were lifestyle factors related to coronary artery calcification. The lifestyle of Japanese people may be related to coronary calcification.

BackgroundVagal nerve stimulation (VNS) benefits patients with heart failure. The afferent vagal nerve mediates cardiopulmonary reflex. We hypothesized that vagal afferent stimulation (AVNS) suppresses sympathetic nerve activity (SNA) and improves heart failure.Methods and ResultsIn 5 ventilated rats, we controlled the isolated, bilateral carotid sinuses pressure (CSP) and measured celiac SNA and AP. In the presence of constant CSP, increasing the voltage of AVNS captured the vagal afferent nerves at 2.7±0.7 volts and dose dependently decreased SNA and AP with a maximal inhibition of SNA at 5.5±1.2 volts. We changed CSP stepwise and measured SNA and AP. AVNS shifted the CSP‐SNA relation (neural arc) downward, whereas unaffected the SNA‐AP relation (peripheral arc). To evaluate the dynamic impacts of AVNS, we randomly stimulated AVNS with binary white noise sequence, and identified the transfer functions from AVNS to SNA (HAVNS‐SNA) and from the SNA to AP (HSNA‐AP). HAVNS‐SNA resembles that of the neural arc, while HSNA‐AP resembles that of the peripheral arc indicating AVNS induces sympathoinhibition just like baroreflex.ConclusionAVNS resets the baroreflex neural arc and induces sympathoinhibition. It may in part attribute to the beneficial impacts of VNS on heart failure.