scholarly journals Human cardiac-specific cDNA array for idiopathic dilated cardiomyopathy: sex-related differences

2008 ◽  
Vol 33 (2) ◽  
pp. 267-277 ◽  
Author(s):  
Georges E. Haddad ◽  
Lori J. Saunders ◽  
Seth D. Crosby ◽  
Maria Carles ◽  
Federica del Monte ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Expression Pattern ◽  
Human Heart ◽  
Gene Expression Pattern ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Transplant Recipients

Idiopathic dilated cardiomyopathy (IDCM) constitutes a large portion of patients with heart failure of unknown etiology. Up to 50% of all transplant recipients carry this clinical diagnosis. Female-specific gene expression in IDCM has not been explored. We report sex-related differences in the gene expression profile of ventricular myocardium from patients undergoing cardiac transplantation. We produced and sequenced subtractive cDNA libraries, using human left ventricular myocardium obtained from male transplant recipients with IDCM and nonfailing human heart donors. With the resulting sequence data, we generated a custom human heart failure microarray for IDCM containing 1,145 cardiac-specific oligonucleotide probes. This array was used to characterize RNA samples from female IDCM transplant recipients. We identified a female gene expression pattern that consists of 37 upregulated genes and 18 downregulated genes associated with IDCM. Upon functional analysis of the gene expression pattern, deregulated genes unique to female IDCM were those that are involved in energy metabolism and regulation of transcription and translation. For male patients we found deregulation of genes related to muscular contraction. These data suggest that 1) the gene expression pattern we have detected for IDCM may be specific for this disease and 2) there is a sex-specific profile to IDCM. Our observations further suggest for the first time ever novel targets for treatment of IDCM in women and men.

P1614Soluble guanylate cyclase as a therapeutic target in heart failure: myocardial gene expression in response to sGC stimulation in pressure overload

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Ruedebusch ◽  
A Benkner ◽  
N Nath ◽  
L Kaderali ◽  
K Klingel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Expression Pattern ◽  
Heart Function ◽  
Gene Expression Pattern ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Marker Genes ◽  
Cgmp Pathway

Abstract Background Heart Failure (HF) is associated with endothelial dysfunction and reduced bioavailability of NO with insufficient stimulation of sGC and reduced production of cGMP. Therefore, the impairment of the NO-sGC-cGMP pathway results in vasoconstriction, platelet aggregation, inflammation, fibrosis and most importantly maladaptive cardiac hypertrophy. The restoration of the NO-sGC -cGMP pathway is an attractive pharmacological target for HF therapy. Purpose Riociguat is an NO independent stimulator of the sGC that sensitizes the sGC to endogenous NO and directly stimulates sGC to produce cGMP. We therefore hypothesized that Riociguat prevents pathological effects occurring during HF. Methods Pressure overload was induced by transverse aortic constriction (TAC) in 8 weeks old male C57Bl6/N mice. Three weeks after TAC when cardiac hypertrophy has developed either Riociguat (RIO; 3 mg/kg) or a Solvent was administered daily for 5 more weeks (n=12 per group). Animals with sham surgery and same drug regime served as controls. The heart function in all groups was evaluated weekly by small animal echocardiography. Eight weeks after surgery, the transcriptome of the left ventricles (LV) of sham and TAC mice were analysed by RNA Sequencing. Differentially expressed genes (DEG) were categorised using Ingenuity Pathway Analysis (IPA). Results TAC resulted in a steady decrease of left ventricular fractional shortening (FS) in the mice until week 3. When Riociguat treatment commenced, the systolic LV function of the TAC+Rio group recovered significantly whereas the solvent group showed a further decline until week 8 (FS 21.4±3.4% vs. 9.5±2%, p<0.001). Both sham groups (Sham+Sol and Sham+Rio) showed no changes in the heart function over timer. Regarding the hypertrophic response to LV pressure overload, Riociguat treatment attenuated significantly the increase of the left ventricular mass (LVM 208.3±15.8mg vs. 148.9±11.8mg, p<0.001) after TAC. In line with the reduced LVM, histological staining showed a significantly reduced fibrosis and myocyte cross sectional area in the TAC+Rio group compared to TAC+Sol group. Regarding the myocardial transcriptome, the treatment with Riociguat resulted in less changes of gene expression pattern after TAC (TAC+Sol vs. Sham+Sol 3160 DEG; TAC+Rio vs. Sham+Rio 2237 DEG). The expression of heart failure marker genes like ANP (Nppa), BNP (Nppb), β-Myosin Heavy Chain (Myh7) and the Collagens 1 and 3 (Col1a1, Col1a2, Col3a1) were significantly decreased in TAC+Rio, when compared to TAC+Sol. IPA analysis revealed that the activation of biological pathways in response to TAC, like actin cytoskeleton- and Integrin signalling, renin-angiotensin or cardiac hypertrophy signalling was attenuated when Riociguat was administered. Conclusion Riociguat attenuates pressure overload induced LV remodelling resulting in less hypertrophy, improved heart function and less alteration of gene expression pattern.

scholarly journals Gene expression of adrenomedullin in failing myocardium: comparison to atrial natriuretic peptide

2002 ◽  
Vol 92 (3) ◽  
pp. 1058-1063 ◽  
Author(s):  
Anselm T. Bäumer ◽  
Christina Schumann ◽  
Bodo Cremers ◽  
Gabi Itter ◽  
Wolfgang Linz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Normal Subjects ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Human Myocardium ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Left Ventricular Myocardium ◽  
End Stage ◽  
Atrial Natriuretic

The expression of adrenomedullin (AM) and atrial natriuretic factor (ANF) were investigated in the myocardium of a rat model of chronic ischemic heart failure (CHF) compared with sham-operated controls. In addition, human myocardium of patients with end-stage heart failure due to idiopathic dilated cardiomyopathy compared with myocardium of normal subjects (NF) was studied. In CHF, similar AM levels but increased ANF expression were observed in left ventricular myocardium, as assessed by semiquantitative PCR. Functional experiments with freshly excised papillary muscles showed no influence of AM on myocardial contractility. In NF human myocardium, the expression of AM mRNA was threefold higher in atrial compared with ventricular tissue. In analogy, ANF mRNA was increased by ∼15-fold in atrial tissue. In dilated cardiomyopathy, the expression of AM was significantly increased in right and left ventricles compared with NF. In parallel, ventricular ANF expression was enhanced.

Surgical therapy for heart failure

2018 ◽  
pp. 157-174
Author(s):  
Stephen Westaby
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Acute Coronary Syndromes ◽  
Symptomatic Relief ◽  
Left Ventricular ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Coronary Syndromes ◽  
Artery Disease ◽  
End Stage ◽  
Age Range

Congestive heart failure affects 23 million people worldwide, and is the final pathway for many diseases that affect the myocardium. Successful intervention in acute coronary syndromes together with improved management of idiopathic dilated cardiomyopathy and dysrhythmia provide an ever-increasing number of advanced heart failure patients spread over a wide age range. In Western countries, coronary artery disease is responsible for about 70% of patients with idiopathic dilated cardiomyopathy and valvular heart disease accounting for 15%. Since 10% of patients older than 65 years suffer systolic left ventricular dysfunction, the numbers with heart failure will double within the next 25 years. For end-stage patients, cardiac transplantation provides the benchmark for increased longevity and symptomatic relief. However, the vast majority of patients are over 65 years of age or are referred with established comorbidity, which precludes transplantation.

Differential atrial and ventricular expression of myocardial BNP during evolution of heart failure

1998 ◽  
Vol 274 (5) ◽  
pp. H1684-H1689 ◽  
Author(s):  
Andreas Luchner ◽  
Tracy L. Stevens ◽  
Daniel D. Borgeson ◽  
Margaret Redfield ◽  
Chi-Ming Wei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Arterial Pressure ◽  
Left Atrium ◽  
Limit Of Detection ◽  
Tissue Concentration ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Lv Function ◽  
Lv Dysfunction

Although brain natriuretic peptide (BNP) of myocardial origin is important in cardiovascular and renal function and as a marker of cardiac dysfunction, the expression of BNP in atrial and ventricular myocardium remains controversial both under normal conditions and in heart failure. We therefore determined left atrial and left ventricular (LV) gene expression and tissue concentration as well as circulating BNP during the evolution of rapid ventricular pacing-induced congestive heart failure (CHF) in the dog. Early LV dysfunction after 10 days of pacing was characterized by impaired LV function but maintained arterial pressure, and overt CHF after 38 days of pacing was characterized by further impaired LV function and decreased systemic arterial pressure. Under normal conditions, cardiac BNP mRNA and cardiac tissue BNP were of atrial origin. In early LV dysfunction, BNP mRNA and tissue BNP were markedly increased in the left atrium in association with an increase in circulating BNP but remained below or at the limit of detection in the LV. In overt CHF, BNP mRNA was further increased in the left atrium and first increased in the LV, together with an increase in LV tissue BNP and a further increase in circulating BNP. In the progression of CHF, early LV dysfunction is characterized by a selective increase in atrial BNP expression in association with increased circulating BNP. Overt CHF is characterized by an additional recruitment of ventricular BNP expression and a further increase in circulating BNP. These studies provide important new insight into the local and temporal regulation of cardiac BNP gene expression during the progression of heart failure and underscore the predominant endocrine role of atrial myocardium under normal conditions and in early LV dysfunction.

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