Ventricular remodeling in a mouse model of myocardial infarction

1998 ◽  
Vol 274 (5) ◽  
pp. H1812-H1820 ◽  
Author(s):  
Richard D. Patten ◽  
Mark J. Aronovitz ◽  
Luz Deras-Mejia ◽  
Natesa G. Pandian ◽  
George G. Hanak ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Body Weight ◽  
Mouse Model ◽  
Sham Group ◽  
Ventricular Remodeling ◽  
Diastolic Pressure ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Body Weight Ratio ◽  
Right Ventricular Mass

We investigated the suitability of studying ventricular remodeling in a mouse model of myocardial infarction (MI). We performed left coronary ligation ( n = 22) or a sham procedure ( n = 21) on normal C57BL/6J mice. Six weeks later, animals underwent echocardiography and hemodynamic evaluation. Left ventricular (LV) volume at a common distending pressure was calculated from passive pressure-volume curves. The MI group exhibited lower systolic blood pressure ( P < 0.05), higher LV end-diastolic pressure ( P < 0.05), and lower peak first derivative of LV pressure (dP/d t, P < 0.05) than the sham group. Mice with moderate (<40%, n = 11) and large (≥40%, n = 11) MIs displayed increased LV mass-to-body weight ratio ( P < 0.02 and P < 0.01, respectively, vs. sham group), whereas only the large-MI group exhibited increased right ventricular mass-to-body weight ratio ( P < 0.01). LV volumes were increased in the moderate-MI group ( P= 0.059 vs. sham group) and to a much greater extent in the large-MI group ( P < 0.0001 vs. sham group). The moderate- and large-MI groups also exhibited increases in LV end-diastolic diameter ( P < 0.03 and P < 0.0001, respectively, vs. sham group) and LV end-systolic diameter ( P< 0.01 and P < 0.0001, respectively, vs. sham group) with decreased fractional shortening ( P < 0.01 for both). These data demonstrate ventricular remodeling in a mouse model of MI and confirm the feasibility of quantifying indexes of remodeling in vivo and postmortem. This model will be of particular usefulness when applied to transgenic strains.

Ovariectomy augments pressure overload-induced hypertrophy associated with changes in Akt and nitric oxide synthase signaling pathways in female rats

2007 ◽  
Vol 293 (6) ◽  
pp. E1606-E1614 ◽  
Author(s):  
Md. Shenuarin Bhuiyan ◽  
Norifumi Shioda ◽  
Kohji Fukunaga
Keyword(s):  
Nitric Oxide ◽  
Body Weight ◽  
Diastolic Pressure ◽  
Heart Function ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Body Weight Ratio

To elucidate the molecular mechanism underlying estrogen-mediated cardioprotection in left ventricular (LV) hypertrophy and remodeling, we analyzed myocardial hypertrophy as well as cardiac function and hypertrophy-related protein expression in ovariectomized, aortic-banded rats. Wistar rats subjected to bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis. Effects on LV morphology and function were assessed using echocardiography, and expression of protein levels was determined by Western blot analysis. The heart-to-body weight ratio was most significantly increased in the OVX-pressure overload (PO) group compared with the OVX group and in the PO group compared with sham. The LV weight-to-body weight ratio was also significantly increased in the OVX-PO group compared with the OVX group and in the PO group compared with sham. The most significant increases in LV end diastolic pressure, LV developed pressure, and ±dp/d tmax were observed in the OVX-PO group compared with the OVX group and represent compensatory phenotypes against hypertrophy. Both endothelial nitric oxide (eNOS) synthase expression and activity was markedly reduced in the OVX-PO group, and protein kinase B (Akt) activity was largely attenuated. Marked breakdown of dystrophin was also seen in hearts of OVX-PO groups. Finally, significantly increased mortality was observed in the OVX-PO group following chronic isoproterenol administration. Our results demonstrate that rats subjected to ovariectomy are unable to compensate for hypertrophy, showed deteriorated heart function, and demonstrated increased mortality. Simultaneous impairment of eNOS and Akt activities and reduced dystrophin by ovariectomy likely contribute to cardiac decompensation during PO-induced hypertrophy in ovariectomized rats.

scholarly journals Progressive chronic heart failure slows the recovery of microvascular O2 pressures after contractions in the rat spinotrapezius muscle

2010 ◽  
Vol 299 (6) ◽  
pp. H1755-H1761 ◽  
Author(s):  
Steven W. Copp ◽  
Daniel M. Hirai ◽  
Leonardo F. Ferreira ◽  
David C. Poole ◽  
Timothy I. Musch
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Chronic Heart Failure ◽  
Diastolic Pressure ◽  
Fiber Type ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Type I ◽  
Body Weight Ratio

Chronic heart failure (CHF) induces muscle fiber-type specific alterations in skeletal muscle O2 delivery and utilization during metabolic transitions. As a result, the recovery of microvascular Po2 (PmvO2) is prolonged in slow-twitch skeletal muscle but not fast-twitch skeletal muscle in rats with CHF. We tested the hypothesis that CHF slows PmvO2 recovery in rat skeletal muscle of a mixed fiber-type analogous to human locomotory muscles and that the degree of slowing correlates with central indexes of heart failure. Healthy control [ n = 6, left ventricular end-diastolic pressure (LVEDP): 10 ± 1 mmHg], moderate CHF ( n = 6, LVEDP: 18 ± 2 mmHg), and severe CHF ( n = 4, LVEDP: 34 ± 2 mmHg) female Sprague-Dawley rats had their right spinotrapezius muscles (41% type I, 7% type IIa, and 52% type IIb and d/x) exposed, and PmvO2 was measured via phosphorescence quenching during 180 s of recovery from 180 s of electrically induced twitch contractions (1 Hz, 4–6 V). CHF progressively slowed the mean response time (MRT; the time to reach 63% of the overall dynamic response) of PmvO2 recovery (MRToff; control: 60.2 ± 6.9, moderate CHF: 72.8 ± 6.6, and severe CHF: 109.8 ± 6.6 s, P < 0.05 for all). MRToff correlated positively with central hemodynamic (LVEDP: r = 0.76, P < 0.01) and morphological (right ventricle-to-body weight ratio: r = 0.74, P < 0.01; and lung weight-to-body weight ratio: r = 0.79, P < 0.01) indexes of heart failure. The present investigation suggests that slowed PmvO2 kinetics during recovery in CHF constitutes a mechanistic link between impaired circulatory and metabolic recovery after contractions in CHF.

Time course of hemodynamic changes in rats with healed severe myocardial infarction

1989 ◽  
Vol 257 (1) ◽  
pp. H289-H296 ◽  
Author(s):  
A. DeFelice ◽  
R. Frering ◽  
P. Horan
Keyword(s):  
Myocardial Infarction ◽  
Blood Flow ◽  
Cardiac Output ◽  
Diastolic Pressure ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Male Rats ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Functional Changes

Male rats were monitored for 8 mo after severe myocardial infarction (MI) to chronicle hemodynamic and left ventricular (LV) functional changes. Blood pressure (BP), heart rate (HR), cardiac output index (CO), regional blood flow, and systemic vascular resistance (SVR) were measured with catheters and radiolabeled microspheres at 4, 7, 10, 20, and 35 wk after coronary artery ligation (n = 10–16/group) or sham operation (control; n = 9–14/group). At 4 wk, 43 +/- 1% of the LV circumference was scarred, peak LV BP, LV dP/dtmax, mean BP, SVR, and HR were 11–38% less than control (P less than 0.05), and LV end-diastolic pressure (LVEDP) was increased by 313% (P less than 0.05). Mean BP, LVEDP, LVBP, and LV dP/dtmax did not further deviate after 4 wk. However, CO and SVR changed progressively and were 67 and 33%, respectively, of control by 35 wk (P less than 0.05) when blood flow to stomach, small intestine, and kidney was 55, 38, and 27% of control. Lung and heart weights were significantly increased by 148 and 22% at 4 wk, and remained elevated, and lung dry weight-to-wet weight ratio was reduced at 7 and 10 wk. Thus the trajectory of rats with healed severe MI reflects progressive cardiac decompensation, cardiac output redistribution, and terminal heart failure.

scholarly journals Low-intensity aerobic interval training attenuates pathological left ventricular remodeling and mitochondrial dysfunction in aortic-banded miniature swine

2010 ◽  
Vol 299 (5) ◽  
pp. H1348-H1356 ◽  
Author(s):  
Craig A. Emter ◽  
Christopher P. Baines
Keyword(s):  
Body Weight ◽  
Exercise Training ◽  
Mitochondrial Dysfunction ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Heart Weight ◽  
Lv Function ◽  
Body Weight Ratio ◽  
Miniature Swine ◽  
Low Intensity

Cardiac hypertrophy in response to hypertension or myocardial infarction is a pathological indicator associated with heart failure (HF). A central component of the remodeling process is the loss of cardiomyocytes via cell death pathways regulated by the mitochondrion. Recent evidence has indicated that exercise training can attenuate or reverse pathological remodeling, creating a physiological phenotype. The purpose of this study was to examine left ventricular (LV) function, remodeling, and cardiomyocyte mitochondrial function in aortic-banded (AB) sedentary (HFSED; n = 6), AB exercise-trained (HFTR, n = 5), and control sedentary ( n = 5) male Yucatan miniature swine. LV hypertrophy was present in both AB groups before the start of training, as indicated by increases in LV end-diastolic volume, LV end-systolic volume (LVESV), and LV end-systolic dimension (LVESD). Exercise training (15 wk) prevented further increases in LVESV and LVESD ( P < 0.05). The heart weight-to-body weight ratio, LV + septum-to-body weight ratio, LV + septum-to-right ventricle ratio, and cardiomyocyte cross-sectional area were increased in both AB groups postmortem regardless of training status. Preservation of LV function after exercise training, as indicated by the maintenance of fractional shortening, ejection fraction, and mean wall shortening and increased stroke volume, was associated with an attenuation of the increased LV fibrosis (23%) and collagen (36%) observed in HFSED animals. LV mitochondrial dysfunction, as measured by Ca2+-induced mitochondrial permeability transition, was increased in HFSED ( P < 0.05) but not HFTR animals. In conclusion, low-intensity interval exercise training preserved LV function as exemplified by an attenuation of fibrosis, maintenance of a positive inotropic state, and inhibition of mitochondrial dysfunction, providing further evidence of the therapeutic potential of exercise in a clinical setting.

Diminished effect of cAMP on Ca2+ accumulation in skinned fibers of hypertrophied rat heart

1994 ◽  
Vol 266 (2) ◽  
pp. H749-H756
Author(s):  
F. Tomita ◽  
A. L. Bassett ◽  
R. J. Myerburg ◽  
S. Kimura
Keyword(s):  
Body Weight ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Adrenergic Stimulation ◽  
Body Weight Ratio ◽  
The Right ◽  
Hypertrophied Ventricle ◽  
Concomitant Exposure

Sarcoplasmic reticulum (SR) Ca2+ uptake is reduced in the hypertrophied ventricle. To determine whether events initiated by beta-adrenergic stimulation are involved, we compared the effects of adenosine 3',5'-cyclic monophosphate (cAMP) on SR Ca2+ uptake between normal and pressure-overloaded hypertrophied hearts using saponin-skinned rat left ventricular muscles. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta for 4–6 wk before study. Age-matched normal rats served as controls. Pressure overload increased the left ventricular weight-to-body weight ratio 60.8%. The SR was loaded by exposing the muscles to 10(-6) M Ca2+ solution; SR Ca2+ release was induced by 5 or 25 mM caffeine, and the amount of Ca2+ released from the SR was estimated by the area under the caffeine-induced transient contraction. Concomitant exposure to 10(-4) M cAMP did not influence caffeine-induced Ca2+ release in either normal or hypertrophied fibers. When 10(-4) M cAMP was applied during the Ca(2+)-loading periods, the amount of Ca2+ accumulated by the SR increased in both normal and hypertrophied fibers. However, the extent of increase was significantly smaller in hypertrophied fibers than in normal fibers [10.9 +/- 1.7 and 27.4 +/- 5.3% in 1 min of Ca2+ loading (P < 0.05), 12.2 +/- 3.2 and 24.7 +/- 3.8% in 4 min of Ca2+ loading (P < 0.05), respectively]. cAMP (10(-4) M) shifted the force-pCa relationship to the right similarly in normal and hypertrophied muscles, and there was no difference in the force-pCa relationship between the two groups either with or without cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased [3H]ouabain binding sites in skeletal muscle of rats with chronic heart failure

1997 ◽  
Vol 83 (1) ◽  
pp. 323-323 ◽  
Author(s):  
Joel G. Pickar ◽  
John P. Mattson ◽  
Steve Lloyd ◽  
Timothy I. Musch
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Chronic Heart Failure ◽  
Exercise Capacity ◽  
Binding Sites ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Body Weight Ratio ◽  
Ouabain Binding

Pickar, Joel G., John P. Mattson, Steve Lloyd, and Timothy I. Musch. Decreased [3H]ouabain binding sites in skeletal muscle of rats with chronic heart failure. J. Appl. Physiol. 83(1): 323–329, 1997.—Abnormalities intrinsic to skeletal muscle are thought to contribute to decrements in exercise capacity found in individuals with chronic heart failure (CHF). Na+-K+-adenosinetriphosphatase (the Na+ pump) is essential for maintaining muscle excitability and contractility. Therefore, we investigated the possibility that the number and affinity of Na+ pumps in locomotor muscles of rats with CHF are decreased. Myocardial infarction (MI) was induced in 8 rats, and a sham operation was performed in 12 rats. The degree of CHF was assessed ∼180 days after surgery. Soleus and plantaris muscles were harvested, and Na+pumps were quantified by using a [3H]ouabain binding assay. At the time of muscle harvest, MI and sham-operated rats were similar in age (458 ± 54 vs. 447 ± 34 days old, respectively). Compared with their sham-operated counterparts, MI rats had a significant amount of heart failure, right ventricular-to-body weight ratio was greater (48%), and the presence of pulmonary congestion was suggested by an elevated lung-to-body weight ratio (29%). Left ventricular end-diastolic pressure was significantly increased in the MI rats (11 ± 1 mmHg) compared with the sham-operated controls (1 ± 1 mmHg). In addition, mean arterial blood pressure was lower in the MI rats compared with their control counterparts. [3H]ouabain binding sites were reduced 18% in soleus muscle (136 ± 12 vs. 175 ± 13 pmol/g wet wt, MI vs. sham, respectively) and 22% in plantaris muscle (119 ± 12 vs. 147 ± 8 pmol/g wet wt, MI vs. sham, respectively). The affinity of these [3H]ouabain binding sites was similar for the two groups. The relationship between the reduction in Na+ pump number and the reduced exercise capacity in individuals with CHF remains to be determined.

Abstract 1393: Inhibition of Cardiac Remodeling by Pravastatin is Associated with Amelioration of Endoplasmic Reticulum Stress

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hui Zhao ◽  
Yulin Liao ◽  
Tetsuo Minamino ◽  
Yoshihiro Asano ◽  
Masanori Asakura ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Er Stress ◽  
Cardiac Remodeling ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Stress Signaling ◽  
Body Weight Ratio ◽  
Stress Signaling Pathway

Background We previously reported that prolonged endoplasmic reticulum (ER) stress contributes to progression from cardiac hypertrophy to heart failure. Statins have an inhibitory effect on cholesterol synthesis, oxidative stresses, protein synthesis and production of inflammatory cytokines, all of which could be associated with ER stress. However, it is unknown whether statins can ameliorate ER stress in heart disease. This study was designed to investigate whether pravastatin could inhibit cardiac remodeling and ameliorate ER stress caused by pressure overload or tumor necrosis factor α (TNF α ). Methods and Results Cardiac hypertrophy was induced by transverse aortic constriction (TAC) for four weeks in C57BL/6 male mice. Either pravastatin (5 mg/kg/d, n=20, TAC+prava group) or its vehicle (n=20) was orally administered to mice. The ER stress signaling pathway was also studied in pressure-overloaded mice hearts and in cultured cardiomyocytes treated with TNF α (10ng/ml) for 24 hours. Four weeks after TAC, both heart-to-body weight ratio (8.68 ± 1.23 in TAC group, 6.92 ± 1.11 in TAC+prava group) and lung-to-body weight ratio (11.08 ± 2.58 in TAC group, 7.92± 3.56 in TAC+prava group) became significantly lower in pravastatin-treated mice than in the TAC group. Left ventricular fractional shortening and left ventricular ejection fraction (LVFS and LVEF) were larger in TAC+prava group (48.0±1.9 % and 80±1.9% respectively) compared with TAC group (LVFS and LVEF, 34.8 ±1.4% and 65 ±3%; P<0.01 VS TAC group each). Markers of ER stress such as an increase in ER chaperones and CHOP expressions and enhanced phosphorylation of eIF2 α were observed in the hearts of TAC mice, while pravastatin treatment significantly blunted these changes. Pravastatin-treated TAC mice also showed a decrease of cardiac apoptosis. Cardiac expression of TNF α was increased in TAC mice, and TNF α induced ER stress in cultured neonatal rat cardiomyocytes, either of which was significantly inhibited by pravastatin. Conclusions These findings indicate that pravastatin inhibits cardiac remodeling in mice subjected to pressure overload, and this action is associated with inhibition of the ER stress signaling pathway.

Lansoprazole alleviates pressure overload-induced cardiac hypertrophy and heart failure in mice by blocking the activation of β-catenin

2019 ◽  
Vol 116 (1) ◽  
pp. 101-113 ◽  
Author(s):  
Hairuo Lin ◽  
Yang Li ◽  
Hailin Zhu ◽  
Qiancheng Wang ◽  
Zhenhuan Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Cardiac Remodelling ◽  
Heart Weight ◽  
Body Weight Ratio

Abstract Aims Proton pump inhibitors (PPIs) are widely used in patients receiving percutaneous coronary intervention to prevent gastric bleeding, but whether PPIs are beneficial for the heart is controversial. Here, we investigated the effects of lansoprazole on cardiac hypertrophy and heart failure, as well as the underlying mechanisms. Methods and results Adult male C57 mice were subjected to transverse aortic constriction (TAC) or sham surgery and then were treated with lansoprazole or vehicle for 5 weeks. In addition, cultured neonatal rat ventricular cardiomyocytes and fibroblasts were exposed to angiotensin II in the presence or absence of lansoprazole. At 5 weeks after TAC, the heart weight/body weight ratio was lower in lansoprazole-treated mice than in untreated mice, as was the lung weight/body weight ratio, while left ventricular (LV) fractional shortening and the maximum and minimum rates of change of the LV pressure were higher in lansoprazole-treated mice, along with less cardiac fibrosis. In cultured cardiomyocytes, lansoprazole inhibited angiotensin II-induced protein synthesis and hypertrophy, as well as inhibiting proliferation of fibroblasts. Lansoprazole decreased myocardial levels of phosphorylated Akt, phosphorylated glycogen synthase kinase 3β, and active β-catenin in TAC mice and in angiotensin II-stimulated cardiomyocytes. After overexpression of active β-catenin or knockdown of H+/K+-ATPase α-subunit, lansoprazole still significantly attenuated myocyte hypertrophy. Conclusion Lansoprazole inhibits cardiac remodelling by suppressing activation of the Akt/GSK3β/β-catenin pathway independent of H+/K+-ATPase inhibition, and these findings may provide a novel insight into the pharmacological effects of PPIs with regard to alleviation of cardiac remodelling.

Age-associated increase in rat ventricular ANP gene expression correlates with cardiac hypertrophy

1995 ◽  
Vol 269 (3) ◽  
pp. H1003-H1008 ◽  
Author(s):  
A. Younes ◽  
M. O. Boluyt ◽  
L. O'Neill ◽  
A. L. Meredith ◽  
M. T. Crow ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Left Atrial ◽  
Northern Blot Analysis ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Mrna Levels ◽  
Body Weight Ratio ◽  
Old Rats

Atrial natriuretic peptide (ANP), a cardiac-specific hormone, is stored in the atria and released in response to atrial stretch. During cardiac hypertrophy, ANP gene expression is markedly upregulated in the left ventricle (LV). Because the hearts of normotensive senescent rats exhibit left atrial (LA) and left ventricular (LV) hypertrophy and dilatation, we examined ANP mRNA levels by Northern blot analysis and ANP peptide concentrations by radioimmunoassay in atria, LVs, and plasma of rats at 2, 6, 18, and 22-24 mo of age. Compared with LVs of 6-mo-old rats, the LV-to-body weight ratio was elevated 30% by 18 mo of age, whereas levels of ANP mRNA were elevated twofold (not significant) and sevenfold (P < 0.05) in the LV of 18- and 22- to 24-mo-old rats, respectively. The concentration of immunoreactive ANP (ir-ANP) exhibited a four- to fivefold increase in LVs of 18- and 22- to 24-mo-old rats compared with values for 6-mo-old rats (43 +/- 4 pmol/g wet wt; means +/- SE). Among 18-and 22- to 24-mo-old rats a significant correlation was observed between ANP peptide concentration and LV hypertrophy (r 2 = 0.64). Levels of ANP mRNA and ir-ANP in the atria exhibited only modest changes with aging.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Interleukin-17 aggravates right ventricular remodeling via activating STAT3 under both normoxia and hypoxia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Huang ◽  
Wei Zhang ◽  
Cai-lian Zhang ◽  
Lei Wang
Keyword(s):  
Body Weight ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Ventricular Remodeling ◽  
Weight Ratio ◽  
Right Ventricular Hypertrophy ◽  
Cardiomyocyte Hypertrophy ◽  
Interleukin 17 ◽  
Diagnostic Biomarker ◽  
Body Weight Ratio

Abstract Objective Proinflammatory cytokine interleukin 17 (IL-17) is involved in ventricular remodeling, mainly of the left ventricle. This study was designed to explore the role of IL-17 played in the pathogenesis of right ventricular hypertrophy (RVH), aiming to provide a novel treatment target or diagnostic biomarker options for improving the care of RVH patients. Methods C57BL/6 mice were maintained in 10% O2 chamber or room air for four weeks. Right ventricular hypertrophy index (RVHI), RV/body weight ratio, pulmonary arteriolar remodeling determined by percent media thickness (%MT), and the cardiomyocyte diameter of RV were evaluated. Mice were treated with exogenous recombinant mouse IL-17 (rmIL-17, 1 μg per dose twice a week) for four weeks. H9c2 cardiomyocytes were cultured and treated with IL-17 (10 ng/mL) and STAT3 inhibitor (10 ng/mL) either under normoxia (21% O2, 5% CO2, 74% N2) or under hypoxia (3% O2, 5% CO2, 92% N2). Cardiomyocyte viability was assessed by Cell counting kit 8 (CCK-8) assay. The mRNA level was detected by RT-PCR, where as the protein expression was measured by Western blot, immunohistochemistry, and immunofluorescent analyses. Results In vivo experiments showed that IL-17 did not affect the pulmonary artery under normoxia, after treatment with rmIL-17, %MT was not changed, while RVHI and the RV/body weight ratio were increased, indicating that IL-17 directly induced right ventricular hypertrophy. In a time-course study, the mice were exposed to hypoxia for 0, 1, 2, 3, 4 weeks, respectively. We found that the expression of IL-17 was gradually upregulated in RV tissue in a time-dependent manner after one week of hypoxia exposure, especially at the third and fourth week. Cardiomyocyte hypertrophy and apoptosis were observed after the exposure of the mice to hypoxia for four weeks, rmIL-17 further aggravated the hypoxia-induced cardiomyocyte hypertrophy and apoptosis. The expression of p-STAT3 in the IL-17-deficient mice was lower than in the wild-type mice. In vitro, IL-17 inhibited cardiomyocyte viability and induced cardiomyocyte apoptosis via STAT3 under both normoxic and hypoxic conditions. Conclusions These findings support a role for IL-17 as a mediator in the pathogenesis RVH, which might be considered as a potential novel anti-inflammation therapeutic strategy or diagnostic biomarker for RVH.

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