Ginseng Reverses Established Cardiomyocyte Hypertrophy and Postmyocardial Infarction-Induced Hypertrophy and Heart Failure

Abstract

Background-A major challenge in the treatment of heart failure is the ability to reverse already-established myocardial remodeling and ventricular dysfunction, with few available pharmacological agents prescribed for the management of heart failure having demonstrated successful reversal of the remodeling and hypertrophic processes. North American ginseng (Panax quinquefolius) has previously been shown to effectively prevent cardiomyocyte hypertrophy and heart failure. Here, we determined whether North American ginseng can reverse established cardiomyocyte hypertrophy in cultured myocytes as well as hypertrophy and left ventricular dysfunction in experimental heart failure secondary to coronary artery occlusion. Methods and Results-Ginseng was administered in drinking water (0.9 g/L) ad libitum to rats after 4 weeks of sustained coronary artery ligation when heart failure was established or to angiotensin II-(100 nmol/L), endothelin-1-(10 nmol/L), or phenylephrine-(10 µmol/L) induced hypertrophic cultured neonatal ventricular cardiomyocytes. Echocardiographic and catheter-based measurements of hemodynamic parameters 4 weeks after starting ginseng treatment (8 weeks postinfarction) revealed nearly complete reversibility of systolic and diastolic abnormalities. Similarly, ginseng administration to hypertrophic cardiomyocytes resulted in a complete reversal to a normal phenotype after 24 hours as determined by cell surface area and expression of molecular markers. The effects of ginseng both in vivo and in cultured cardiomyocytes were associated with reversal of calcineurin activation and reduced nuclear translocation of the transcription factor NFAT3 (nuclear factor of activated T cells 3) in cultured myocytes. Moreover, the beneficial effect of ginseng was associated with normalization in the gene expression of profibrotic markers, including collagen (I and III) and fibronectin. Conclusions-This study demonstrates a marked ability of ginseng to reverse cardiac hypertrophy, myocardial remodeling, and heart failure, which was associated with and likely mediated by reversal of calcineurin activation. Ginseng may offer a potentially effective approach to reverse the myocardial remodeling and heart failure processes, particularly in combination with other treatment modalities.

Probiotic Administration Attenuates Myocardial Hypertrophy and Heart Failure After Myocardial Infarction in the Rat

“…9 Briefly, rats were anesthetized with pentobarbital sodium (50 mg/kg body weight [bw], IP), intubated, and artificially ventilated using a rodent respirator (model 683, Harvard Apparatus). A left thoracotomy was performed and the heart was gently exposed.…”

“…Rats were anesthetized with 2% isoflurane and echocardiography was performed as previously described 9 using a Vevo 770 high-resolution in vivo microimaging system equipped with a real-time microvisualization scan head of 17.5 MHz (VisualSonics, Toronto, Ontario, Canada). M-mode 2-dimensional (2D) echocardiography images were obtained from the parasternal short axis.…”

“…An anterior thoracotomy was performed and the LV was catheterized retrogradely via the right carotid artery using a 2.0F P-V Mikro-Tip catheter (Millar Instruments, Houston, TX) as previously described. 9 Left ventricular pressure-volume relationships (P-V loops) were obtained by increasing afterload by a gradual occlusion of the ascending aorta.…”

“…Aliquots of 100 μL of GR-1 in skim milk or skim milk only for control groups were stored at −20°C until use. GR-1 was administered in the drinking water ad libitum immediately after completion of surgery to provide an approximate daily dose of 1×10 9 CFUs based on water consumption of ≈50 mL/d. For most studies, treatments were performed for the entire 6-week follow-up period, although an additional study entailed the probiotic being withdrawn after 4 weeks and replaced with control drinking water for the remaining 2 weeks.…”

A systems genetics approach identifiesTrp53inp2as a link between cardiomyocyte glucose utilization and hypertrophic response

“…Protocol for changes in cell size was adapted from a previous publication (41). Briefly, cardiomyocytes were treated as indicated and then washed in PBS (3 times), fixed using 4% PFA, and imaged under phase contrast at ϫ20 magnification.…”