Dynamic changes of gene expression in hypoxia-induced right ventricular hypertrophy

2004 ◽  
Vol 286 (3) ◽  
pp. H1185-H1192 ◽  
Author(s):  
Saumya Sharma ◽  
Heinrich Taegtmeyer ◽  
Julia Adrogue ◽  
Peter Razeghi ◽  
Shiraj Sen ◽  
...  
Keyword(s):  
Right Ventricle ◽  
Right Ventricular ◽  
Pyruvate Dehydrogenase ◽  
Hypobaric Hypoxia ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Pyruvate Dehydrogenase Kinase ◽  
Myosin Isoforms ◽  
Pyruvate Dehydrogenase Kinase 4 ◽  
The Right

Hypobaric hypoxia induces right ventricular hypertrophy. The relative contribution of pulmonary hypertension, decreased arterial oxygen, and neuroendocrine stimulation to the transcriptional profile of hypoxia-induced right ventricular hypertrophy is unknown. Whereas both ventricles are exposed to hypoxia and neuroendocrine stimulation, only the right ventricle is exposed to increased load. We postulated that right ventricular hypertrophy would reactivate the fetal gene transcriptional profile in response to increased load. We measured the expression of candidate genes in the right ventricle of rats exposed to hypobaric hypoxia (11% O2) and compared the results with the left ventricle. Hypoxia induced right ventricular hypertrophy without fibrosis. In the right ventricle only, atrial natriuretic factor transcript levels progressively increased starting at day 7. Metabolic genes were differentially regulated, suggesting a substrate switch from fatty acids to glucose during early hypoxia and a switch back to fatty acids by day 14. There was also a switch in myosin isogene expression and a downregulation of sarcoplasmic/endoplasmic ATPase 2a during early hypoxia, whereas later, both myosin isoforms and SERCA2a were upregulated. When the right and left ventricle were compared, the transcript levels of all genes, except for myosin isoforms and pyruvate dehydrogenase kinase-4, differed dramatically suggesting that all these genes are regulated by load. Our findings demonstrate that hypoxia-induced right ventricular hypertrophy transiently reactivates the fetal gene program. Furthermore, myosin iso-gene and pyruvate dehydrogenase kinase-4 expression is not affected by load, suggesting that either hypoxia itself or neuroendocrine stimulation is the primary regulator of these genes.

Activation of the right ventricular endothelin (ET) system in the monocrotaline model of pulmonary hypertension: response to chronic ETA receptor blockade

2003 ◽  
Vol 105 (6) ◽  
pp. 647-653 ◽  
Author(s):  
Jean-François JASMIN ◽  
Peter CERNACEK ◽  
Jocelyn DUPUIS
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Lower Percentage ◽  
Receptor Blockade ◽  
Eta Receptor ◽  
Eta Receptor Antagonist ◽  
The Right

Although activation of the endothelin (ET) system contributes to pulmonary hypertension, modifications of the cardiopulmonary ET system and its responses to chronic ET receptor blockade are not well known. To investigate this, rats were injected with monocrotaline (60 mg/kg intraperitoneal) or saline, followed with treatment with the selective ETA receptor antagonist LU135252 (LU; 50 mg·kg-1·day-1) or with saline. After 3 weeks, haemodynamics, cardiac hypertrophy, ET-1 levels and cardiopulmonary ET-receptor-binding profile were evaluated. Monocrotaline (n=7) elicited marked pulmonary hypertension and right ventricular hypertrophy compared with controls (n=8). Both variables were substantially attenuated by LU therapy (n=8; P<0.05 for both). After monocrotaline, right ventricular ET-1 levels were more significantly increased than in the left ventricle (+198% compared with +127%; P<0.05). ETB receptor density was augmented (3-fold) in the right ventricle, whereas that of ETA receptors was not affected. LU treatment also significantly attenuated these alterations (P<0.05). In the lungs, ET-1 levels were not increased after monocrotaline, whereas the balance of ETB to ETA receptors was altered, with a trend toward a lower percentage of ETB than in the control rats. LU treatment did not affect these variables in the lungs. Therefore monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy are associated with the up-regulation of ET-1 and ETB receptors in the right ventricle. These alterations are attenuated with the reduction of pulmonary hypertension and right ventricular hypertrophy after chronic blockade of the ETA receptors, supporting the role of the ET system in right ventricular hypertrophy.

Cystamine Treatment Fails to Prevent the Development of Pulmonary Hypertension in Chronic Hypoxic Rats

2021 ◽  
pp. 1-15
Author(s):  
Lars K. Markvardsen ◽  
Lene D. Sønderskov ◽  
Christine Wandall-Frostholm ◽  
Estéfano Pinilla ◽  
Judit Prat-Duran ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Lung Tissue ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Right Ventricular Hypertrophy ◽  
Ventricular Systolic Pressure ◽  
Pulmonary Arterial ◽  
The Right

<b><i>Introduction:</i></b> Pulmonary hypertension is characterized by vasoconstriction and remodeling of pulmonary arteries, leading to right ventricular hypertrophy and failure. We have previously found upregulation of transglutaminase 2 (TG2) in the right ventricle of chronic hypoxic rats. The hypothesis of the present study was that treatment with the transglutaminase inhibitor, cystamine, would inhibit the development of pulmonary arterial remodeling, pulmonary hypertension, and right ventricular hypertrophy. <b><i>Methods:</i></b> Effect of cystamine on transamidase activity was investigated in tissue homogenates. Wistar rats were exposed to chronic hypoxia and treated with vehicle, cystamine (40 mg/kg/day in mini-osmotic pumps), sildenafil (25 mg/kg/day), or the combination for 2 weeks. <b><i>Results:</i></b> Cystamine concentration-dependently inhibited TG2 transamidase activity in liver and lung homogenates. In contrast to cystamine, sildenafil reduced right ventricular systolic pressure and hypertrophy and decreased pulmonary vascular resistance and muscularization in chronic hypoxic rats. Fibrosis in the lung tissue decreased in chronic hypoxic rats treated with cystamine. TG2 expression was similar in the right ventricle and lung tissue of drug and vehicle-treated hypoxic rats. <b><i>Discussion/Conclusions:</i></b> Cystamine inhibited TG2 transamidase activity, but cystamine failed to prevent pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial muscularization in the chronic hypoxic rat.

scholarly journals P270 Complex cyanotic heart disease in adult patient with down syndrome accompanied by mild pulmonary hypertension

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A Siama ◽  
P Fountoulakis ◽  
A Tsoukas ◽  
A J Manolis
Keyword(s):  
Down Syndrome ◽  
Heart Disease ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Cyanotic Heart Disease ◽  
History Of ◽  
The Right ◽  
Bidirectional Flow

Abstract Funding Acknowledgements No funding Introduction Patients with Down syndrome and complex unrepaired cyanotic heart disease have impaired life expectancy. The clinical status of each patient depends both on the primary lesion type as well as the cummulative haemodynamic burden in the cardiovascular system. Assessment of an adult patient with complex congenital heart disease that has not been surgically repaired presents several challenges since initial haemodynamic parameters and compensatory mechanisms have to be taken into account. Case presentation A 43 year old male patient with known history of Down syndrome and no regular follow up presented to the Outpatient Department of our hospital to undergo pre-operative control for minor soft tissue surgery. The patient exhibited typical morphological features of Down syndrome as well as central cyanosis and digital clubbing. On auscultation a holosystolic type murmur 3/6 on the 3rd left parasternal border was audible. His blood gases revealed hypoxia and mild metabolic acidosis. Electrocardiogram displayed right axis deviation and signs of right ventricular hypertrophy. Transthoracic echocardiography demonstrated a large perimembranous ventricular septal defect (VSD) with normal anatomy and function of the aortic valve and no overiding aorta. Of note was excessive infundibular subpulmonary stenosis which resulted in a functionally double chambered right ventricle. Left ventricle was of normal diamater with good overall systolic function while the right ventricle was non-dilated with significant hypertrophy. Intracavitary gradient was estimated at 60 mmHg. Continuous Doppler showed mild mitral regurgitaion and mild tricuspid regurgitaion with estimated systolic pulmonary pressure of 40 mmHg. Bidirectional flow with low velocities at the level of the defect was recorded. Inferior vena cava was mildly dilated with normal respiratory variation. Discussion/ Conclusion: The natural history of large VSDs results in progressive dilatation of the right ventricle, the left ventricle and the left atrium with gradually increasing pylmonary vascular resistance and development of pulmonary hypertension, followed by right ventricular hypertrophy, flow reversal and Eisenmenger syndrome. However when RVOT obstruction at any level coexists, significant right ventricular hypertrophy develops and the incresed right ventricular systolic pressures acts protectively by minimizing the shunt at the VSD level. Thus a restrictive VSD due to a functionally double chambered right ventricle created a very fragile balance; a cyanotic heart disease with mild bidirectional flow depending on preload and afterload conditions that survived to adulthood. Abstract P270 Figure. Complex unrepaired CHD

Transient severe isolated right ventricular hypertrophy in neonates

2003 ◽  
Vol 13 (4) ◽  
pp. 384-386 ◽  
Author(s):  
Munesh Tomar ◽  
Sitaraman Radhakrishnan ◽  
Savitri Shrivastava
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Function ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Posterior Wall ◽  
Right Ventricular Hypertrophy ◽  
Pulmonary Vasculature ◽  
Normal Thickness ◽  
The Right

We report two instances of transient isolated right-sided myocardial hypertrophy in patients with an intact ventricular septum, normal thickness of the posterior wall of the left ventricle, and normal ventricular function, diagnosed by echocardiography on the third day of life. The two neonates, born at 36 and 38 weeks gestation respectively, had perinatal distress. Both were diagnosed as having isolated right ventricular hypertrophy with mild pulmonary hypertension, which disappeared in both cases within 8 weeks without any specific therapy. Though the cause of the ventricular hypertrophy remains unclear, we believe that it is the consequence of remodeling of pulmonary vasculature secondary to acute perinatal distress, resulting in persistent pulmonary hypertension and producing pressure overload on the right ventricle, and hence right ventricular hypertrophy. The finding of early and transient right ventricular hypertrophy, with normal left-sided structures and normal ventricular function, has thus far failed to gain attention in the paediatric cardiologic literature.

CLINICAL CONFERENCE

PEDIATRICS ◽  
1957 ◽  
Vol 19 (6) ◽  
pp. 1139-1147
Author(s):  
Mary Allen Engle
Keyword(s):  
Blood Flow ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Pulmonary Blood Flow ◽  
Ventricular Hypertrophy ◽  
Pulmonary Valve ◽  
Muscular Tissue ◽  
Pulmonic Stenosis ◽  
Infundibular Stenosis ◽  
The Right

Dr. Engle: When pulmonic stenosis occurs as an isolated congenital malformation of the heart, it usually is due to fusion of the valve cusps into a dome with a small hole in the center. In Figure 1 the pulmonary artery has been laid open so that one can see the three leaflets of the pulmonary valve are completely fused, and that there is only a small, central, pinpoint opening which permits blood to leave the right ventricle and enter the pulmonary circulation. Valvular pulmonic stenosis is much more common than subvalvular or infundibular stenosis, where the obstruction to pulmonary blood flow lies within the substance of the right ventricle. There it may be due to a diaphragm of tissue which obstructs the outflow of the right ventricle, or to an elongated narrow tunnel lined with thickened endocardium, or to a ridge of fibrous or muscular tissue just beneath the pulmonary valve. The changes in the cardiovascular system which result from obstructed pulmonary blood flow are so characteristic that they permit the ready recognition of this condition. Proximal to the constriction, these changes manifest the burden placed on the right ventricle, which enlarges and hypertrophies. On physical examination this is demonstrated by the precordial bulge and tapping impulse just to the left of the sternum, where the rib cage overlies the anterior (right) ventricle. Radiographically, both by fluoroscopy and in roentgenograms in the frontal and both oblique views, right ventricular enlargement is seen. In the electrocardiogram, the precordial leads show a pattern of right ventricular hypertrophy.

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