Abstract 1954: Activation of Endothelial Cells in Conduit Veins of Dogs With Heart Failure and Veins of Normal Dogs Following Vascular Stretch by Acute Volume Loading

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paolo Colombo ◽  
Sharad Rastogi ◽  
Duygu Onat ◽  
Valerio Zaca ◽  
Hani N Sabbah
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Venous Pressure ◽  
Endothelial Activation ◽  
Jugular Veins ◽  
Novel Approach ◽  
Tnf Α ◽  
Fluid Load ◽  
Cox 2 ◽  
Morbid Conditions

Background: Endothelial dysfunction is an independent predictor of poor prognosis in patients with heart failure (HF). Using a novel approach of endovascular endothelial cell (EC) sampling, we previously showed that ECs collected from conduit veins using J-wires are activated in patients with HF as evidenced by increased expression of pro-inflammatory genes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The underlying cause(s) of this endothelial activation and dysfunction is not known. In this study, we tested the hypothesis that the HF state itself and the vascular strain associated with congestion can both account for these findings. Methods: We studied 6 normal (NL) dogs (LV ejection fraction >50%, central venous pressure (CVP) ~ 8 mmHg) and 6 dogs with HF (ejection fraction ~ 30%, CVP ~9 mmHg) produced by intracoronary microembolizations. This model of HF manifests the disease syndrome in the absence of other co-morbid conditions often present in patients with CHF. NL dogs were studied at baseline and 1 hr after rapid fluid load (500 ml Dextran-40) resulting in CVP>20 mmHg. ECs were scraped from jugular veins. mRNA was analyzed by RT-PCR and quantified in densitometric units (du). Results: Data are shown in the table . Endothelial iNOS and COX-2 were increased in HF dogs compared to NL. Tissue necrosis factor (TNF)-α, early growth response gene (EGR-1), receptor for advanced glycation end products (RAGE) and glutathione peroxidase (GPx) were also up-regulated in HF. In NL dogs, fluid load increased iNOS, COX-2, TNF-α, Egr-1, RAGE and GPx to levels that approached those of HF. Conclusions: The HF state itself, in the absence of other co-morbid conditions, and vascular stretch are both sufficient to activate venous ECs in dogs in a manner consistent with that seen in patients with HF. As such, molecular measures of EC dysfunction may potentially serve as “biomarkers” of severity of HF and possibly of impending decompensation.

Abstract 14244: Circulating Vascular Cell Adhesion Molecule-1 and Incident Heart Failure: The Multi- Ethnic Study of Atherosclerosis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ravi B Patel ◽  
Laura A Colangelo ◽  
Suzette J Bielinski ◽  
Nicholas B Larson ◽  
Jingzhong Ding ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Adhesion ◽  
Ejection Fraction ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Endothelial Activation ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Vascular Cell Adhesion Molecule ◽  
Cell Adhesion Molecule 1

Background: Serum levels of vascular cell adhesion molecule-1 (VCAM-1) are reflective of endothelial activation, a pathologic process that is associated with subclinical cardiac dysfunction. While VCAM-1 has been implicated in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFpEF), the prospective association of VCAM-1 with clinically overt HF is unclear. Methods: In the Multi-Ethnic Study of Atherosclerosis, we evaluated the association of VCAM-1 at Exam 2 (2002-2004) with incident HF across ejection fraction (EF) categories (HFpEF and HF with reduced EF [HFrEF]) after adjustment for cardiovascular risk factors. Incident HF was adjudicated as first hospitalization for symptomatic HF, requiring specific clinical and/or imaging criteria. Results: Of 2,298 participants (mean age: 63.0 years, female: 53%), those with higher VCAM-1 were more likely white race, had higher blood pressure, and lower renal function. Over a median of 16.0 years, there were 102 HF events (HFpEF = 65; HFrEF = 37) ( Figure ). After covariate adjustment, VCAM-1 was independently associated with incident HF ( Table ). Upon evaluation of HF subtypes, VCAM-1 was associated with incident HFpEF, and risk effect estimates were consistent for incident HFrEF. The association of VCAM-1 with incident HF was consistent across the spectrum of age, sex, and BMI. Conclusion: In a multiethnic cohort, VCAM-1 was independently associated with incident HF over long-term follow up. These findings suggest a potential role for endothelial activation in driving clinical HF. Lifestyle and pharmacologic therapies that decrease endothelial activation may prevent the progression to clinical HF.

scholarly journals Effect of Shenfu Qiangxin on the expression of TGF-β/Smads signaling pathway-related molecules in myocardium of rats with heart failure

2019 ◽  
Vol 17 ◽  
pp. 205873921985285
Author(s):  
Li Xiong ◽  
Guobo Xie ◽  
Binhua Luo ◽  
Zhiliang Mei
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Signaling Pathway ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Tgf Beta ◽  
Model Group ◽  
Ventricular Ejection Fraction ◽  
Tnf Α ◽  
Losartan Group

This study aims to evaluate the effect of Shenfu Qiangxin on TGF-β/Smads signaling pathway-related molecules in myocardial tissue of rats with heart failure. Five rats were selected as sham-operated group, while another 15 rats with heart failure were divided into three groups, including model group, losartan group, and Shenfu Qiangxin group. Rats in losartan group were given losartan intragastric intervention, the rats in Shenfu Qiangxin group were given Shenfu Qiangxin mixture intervention, while rats in another two groups were given equal volume of sterile saline intervention. During the treatment, the levels of B-type brain natriuretic peptide (BNP), lactate dehydrogenase (LDH), free fatty acids (FFA), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and TGF-β/Smads signaling pathway were measured in rats. Compared with model group, the expression of ejection fraction (EF), left ventricular ejection fraction (LVSP), TGF-β 1, Smad2, and Smad3 significantly decreased in sham-operated group, losartan group, and Shenfu Qiangxin group, while left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVDd), left ventricular end-diastolic pressure (LVEDP), BNP, LDH, FFA, TNF-α, and IL-6 levels increased ( P < 0.05). Compared with sham-operated group, the expression of EF, LVSP, TGF-beta 1, Smad2, and Smad3 dramatically decreased in losartan group, Shenfu Qiangxin group, but LVEDV, LVDd, LVEDP, BNP, LDH, FFA, TNF-α, and IL-6 levels increased ( P < 0.05). Compared with losartan group, the expression of EF, LVSP, TGF-beta 1, Smad2, and Smad3 upregulated in Shenfu Qiangxin group, while LVEDV, LVDd, LVEDP, BNP, LDH, FFA, TNF-α, and IL-6 levels downregulated ( P < 0.05). Consequently, Shenfu Qiangxin could effectively improve the heart function of rats with heart failure, and play an anti-heart failure role by regulating the expression of related molecules of TGF-β/Smads signaling pathway.

scholarly journals MO062CHRONIC KIDNEY DISEASE, INFLAMMATION, AND HEART FAILURE WITH PRESERVED EJECTION FRACTION: A RENAL-CARDIO AXIS?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Alejandro Chade ◽  
Maxx Williams ◽  
Jason Engel ◽  
Gene Bidwell
Keyword(s):  
Heart Failure ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Left Ventricular ◽  
Swine Model ◽  
Preserved Ejection Fraction ◽  
Renal Inflammation ◽  
Tnf Α

Abstract Background and Aims Inflammation contributes to progressive renal dysfunction and increases cardiovascular mortality of patients with chronic kidney disease (CKD). The association of CKD and heart failure with preserved ejection fraction (HFpEF) is observed in up to 50%, suggesting the possibility of a shared pathophysiology. CKD and HFpEF are commonly associated with inflammation. Using a novel swine model of CKD and HFpEF, we propose that a renal-cardio inflammatory axis drives diastolic dysfunction and HFpEF in CKD and that targeting renal inflammation will improve cardiac health and reduce cardiovascular risk. Methods We developed a biopolymer-fused peptide of nuclear-factor kappa (NFk)B (ELP-p50i) that we show it blocks its activity in vitro and in vivo. NFkB is a key pro-inflammatory transcription factor that is upregulated in CKD. To test our hypothesis, we induced CKD in 10 pigs via bilateral renovascular disease and dyslipidemia. Pigs were observed for 6 weeks, renal hemodynamics quantified (multi-detector CT), then randomized to single intra-renal ELP-p50i or placebo (n=5 each), and studies repeated 8 weeks later accompanied by echocardiographic assessment. Blood pressure was continuously measured (telemetry). Blood was collected to measure circulating TNF-α and biomarkers of HF (ANP, BNP). Furthermore, kidneys and hearts were used to quantify expression of factors involved in NFkB signaling. Results CKD led to a significant loss of renal function, accompanied by left ventricular hypertrophy and diastolic dysfunction with pEF, increased renal mRNA expression of TNF-α and canonical and non-canonical mediators of NFkB signaling, and elevated systemic TNF-α, ANP, and BNP, indicating renal and cardiac dysfunction. Most of these changes were improved after intra-renal ELP-p50i, although cardiac inflammatory signaling was unchanged (Figure) suggesting the kidney as a source of inflammation that can target the heart in CKD. Conclusion We show that a renal anti-inflammatory strategy via targeted inhibition of renal NFkB improves renal and cardiac function in CKD, suggesting an inflammatory renal-cardio axis. The translational pathological features of CKD and HFpEF combined with the predictive power of the model may contribute to advance the field towards new treatments targeting renal inflammation to reduce cardiovascular risk in CKD.

scholarly journals Cardiorenal Syndrome Caused by Heart Failure with Preserved Ejection Fraction

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Chiara Lazzeri ◽  
Serafina Valente ◽  
Roberto Tarquini ◽  
Gian Franco Gensini
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Venous Pressure ◽  
Renin Angiotensin System ◽  
Cardiorenal Syndrome ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Optimal Therapeutic Strategy

Since cardiorenal dysfunction is usually secondary to multiple factors acting in concert (and not only reduced cardiac output) in the present paper we are going to focus on the interrelationship between heart failure with normal ejection fraction and the development of cardiorenal syndrome. The coexistence of renal impairment in heart failure with preserved ejection fraction (CRS type 2 and 4) is common especially in older females with hypertension and/or diabetes. It can be hypothesized that the incidence of this disease association is growing, while clinical trials enrolling these patients are still lacking. The main mechanisms thought to be involved in the pathophysiology of this condition are represented by the increase of intra-abdominal and central venous pressure and the activation of the renin-angiotensin system. Differently from CRS in heart failure with reduced ejection fraction, the involvement of the kidney may be under-diagnosed in patients with heart failure and preserved ejection fraction and the optimal therapeutic strategy in this condition, though challenging, is far to be completely elucidated. Further studies are needed to assess the best therapeutic regimen in patients with renal dysfunction (and worsening) and heart failure and preserved ejection fraction.

scholarly journals Sacubitril-Valsartan Improves Conduit Vessel Function and Functional Capacity, and Reduces Inflammation in Heart Failure with Reduced Ejection Fraction

2020 ◽  
Author(s):  
Kanokwan Bunsawat ◽  
Stephen M. Ratchford ◽  
Jeremy K. Alpenglow ◽  
Soung Hun Park ◽  
Catherine L. Jarrett ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Functional Capacity ◽  
Vascular Function ◽  
Left Ventricular Ejection ◽  
Peripheral Vascular ◽  
Reduced Ejection Fraction ◽  
6Mwt Distance ◽  
Tnf Α ◽  
Conduit Vessel

The PARADIGM-HF trial identified a marked reduction in the risk of death and hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril-valsartan, but the physiologic processes underpinning these improvements are unclear. We tested the hypothesis that treatment with sacubitril-valsartan improves peripheral vascular function, functional capacity, and inflammation in patients with HFrEF. We prospectively studied patients with HFrEF (n=11, 10M/1F, left ventricular ejection fraction 27±8%) on optimal, guideline-directed medical treatment who were subsequently prescribed sacubitril-valsartan (open-label, uncontrolled, and unblinded). Peripheral vascular function (brachial artery flow-mediated dilation (FMD, conduit vessel function) and reactive hyperemia (RH, microvascular function)), functional capacity (six-minute walk test (6MWT) distance), and the pro-inflammatory biomarkers, tumor necrosis factor-alpha (TNF-α) and interleukin-18 (IL-18) were obtained at baseline and again at 1, 2, and 3 months of treatment. %FMD improved after 1 month of treatment, and this favorable response persisted for months 2 and 3 (baseline: 3.25±1.75%; 1mo: 5.23±2.36%; 2mo: 5.81±1.79%; 3mo: 6.35±2.77%), while RH remained unchanged. 6MWT distance increased at months 2 and 3 (baseline: 420±92 m; 1mo: 436±98 m; 2mo: 465±115 m; 3mo: 460±110 m), and there was a sustained reduction in TNF-α (baseline: 2.38±1.35 pg/mL; 1mo: 2.06±1.52 pg/mL; 2mo: 1.95±1.34 pg/mL; 3mo: 1.92±1.37 pg/mL) and a reduction in IL-18 at months 3 (baseline: 654±150 pg/mL; 1mo: 595±140 pg/mL; 2mo: 601±176 pg/mL; 3mo: 571±127 pg/mL). This study provides new evidence for the potential of this new drug class to improve conduit vessel function, functional capacity, and inflammation in patients with HFrEF.

scholarly journals Circulating Vascular Cell Adhesion Molecule‐1 and Incident Heart Failure: The Multi‐Ethnic Study of Atherosclerosis (MESA)

2020 ◽  
Vol 9 (22) ◽  
Author(s):  
Ravi B. Patel ◽  
Laura A. Colangelo ◽  
Suzette J. Bielinski ◽  
Nicholas B. Larson ◽  
Jingzhong Ding ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Cardiovascular Risk ◽  
Ejection Fraction ◽  
Cell Adhesion Molecule ◽  
Endothelial Activation ◽  
Vascular Cell Adhesion ◽  
Vascular Cell ◽  
Reduced Ejection Fraction ◽  
Cell Adhesion Molecule 1

Background Serum levels of vascular cell adhesion molecule‐1 (VCAM‐1) are reflective of endothelial activation. Although VCAM‐1 has been implicated in the pathogenesis of heart failure with preserved ejection fraction (HFpEF), the prospective association of VCAM‐1 with development of clinically overt heart failure (HF) across ejection fraction categories is unclear. Methods and Results In MESA (the Multi‐Ethnic Study of Atherosclerosis), we evaluated the association of VCAM‐1 at examination 2 (2002–2004) with incident HF (HFpEF and HF with reduced ejection fraction) after adjustment for cardiovascular risk factors. Incident HF was independently adjudicated as first hospitalization for symptomatic HF. Among 2297 participants (mean age, 63 years; women, 53%), those with higher VCAM‐1 were more likely to be White race, had higher blood pressure, and had lower kidney function. Over a median of 14.4 years, there were 102 HF events (HFpEF=65; HF with reduced ejection fraction=37). After covariate adjustment, each doubling of VCAM‐1 was associated with incident HF (hazard ratio [HR], 1.94; 95% CI, 1.17–3.23; P =0.01). This association appeared stronger among current/former smokers compared with never smokers. On evaluation of HF subtypes, VCAM‐1 was associated with incident HFpEF (HR, 1.97; 95% CI, 1.04–3.72; P =0.04) but not with incident HF with reduced ejection fraction, although risk estimates were consistent (HR, 1.82; 95% CI, 0.79–4.21; P =0.16). Conclusions In a multiethnic cohort, VCAM‐1 was significantly associated with incident HF over long‐term follow‐up. These findings suggest a potential role for endothelial activation in driving clinical HF, and specifically HFpEF. Therapies that decrease endothelial activation may prevent the progression from cardiovascular risk factors to clinical HF.

scholarly journals ARNi: A Novel Approach to Counteract Cardiovascular Diseases

2019 ◽  
Vol 20 (9) ◽  
pp. 2092 ◽  
Author(s):  
Massimo Volpe ◽  
Speranza Rubattu ◽  
Allegra Battistoni
Keyword(s):  
Heart Failure ◽  
Cardiovascular Diseases ◽  
Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
New Class ◽  
Novel Approach ◽  
Hormonal System ◽  
Therapeutic Tools ◽  
And Control ◽  
New Evidence

Cardiovascular diseases (CVDs) still represent the greatest burden on healthcare systems worldwide. Despite the enormous efforts over the last twenty years to limit the spread of cardiovascular risk factors, their prevalence is growing and control is still suboptimal. Therefore, the availability of new therapeutic tools that may interfere with different pathophysiological pathways to slow the establishment of clinical CVDs is important. Previously, the inhibition of neurohormonal systems, namely the renin–angiotensin–aldosterone system (RAAS) and the sympathetic nervous system, has proven to be useful in the treatment of many CVDs. Attempts have recently been made to target an additional hormonal system, that of the natriuretic peptides (NPs), which, when dysregulated, can also play a role in the development CVDs. Indeed, a new class of drug, the angiotensin receptor–neprilysin inhibitors (ARNi), has the ability to counteract the effects of angiotensin II as well as to increase the activity of NPs. ARNi have already been proven to be effective in the treatment of heart failure with reduced ejection fraction. New evidence has suggested that, in the next years, the field of ARNi application will widen to include other CVDs, such as heart failure, with preserved ejection fraction and hypertension.

scholarly journals HUBUNGAN KADAR TNF-α DENGAN FRAKSI EJEKSI PADA PASIEN GAGAL JANTUNG KRONIK DI BLU/RSUP PROF. DR. R.D. KANDOU

e-CliniC ◽  
2014 ◽  
Vol 2 (1) ◽  
Author(s):  
Leonard K. Moningkey
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Negative Correlation ◽  
Clinical Results ◽  
P Value ◽  
Cross Sectional ◽  
Tnf Α ◽  
Cross Sectional Design ◽  
Degrees Of Severity

Abstract: In patients with chronic heart failure, increases of the TNF-α and IL-6 concentrations are correlated with the degrees of severity of heart failure symptoms and clinical results. This study aimed to obtain the correlation between the concentration of TNF-α and the ejection fraction (EF) among patients with chronic heart failure. This was an analytic study with a cross-sectional design. As samples, there were 30 patients with chronic heart failure at Prof. Dr. R. D. Kandou Hospital Manado from November – December 2012. The results showed that based on TNF-α concentration, there were 15 patients with EF 40-50 %; 11 patients with EF 31-39 %; and 4 patients with EF ≤ 30 %. The Spearman–rho test showed that there was a negative correlation between TNF-α concentrations and Ejection Fraction among patients with chronic heart failure at Prof. Dr. R. D. Kandou Hospital Manado, with a P value of 0.658. Conclusion: Although there was a negative correlation between TNF-α concentrations and Ejection Fraction among patients with chronic heart failure at Prof. Dr. R. D. Kandou Hospital Manado, it was not statistically significant.Keywords: chonic heart failure, left ventricle ejection fraction, TNF-α.Abstrak: Pada penderita gagal jantung kronik, terjadi peningkatan kadar sitokin pro inflamasi dalam plasma, termasuk TNF-α dan IL-6, berkorelasi dengan derajat keparahan gejala gagal jantung dan hasil klinis. Penelitian ini bersifat analitik dengan pendekatan cross sectional. Sampel penelitian ialah pasien gagal jantung kronis (GJK) di BLU/RSUP Prof. Dr. R.D. Kandou Manado. Penelitian dilakukan pada bulan November-Desember 2012 dengan jumlah sampel sebanyak 30 pasien. Hasil penelitian memperlihatkan bahwa distribusi pasien GJK menurut TNF-α terbanyak pada pasien dengan fraksi ejeksi 40-50% yaitu 15 orang (50%), dan paling rendah pada pasien dengan fraksi ejeksi <30% yaitu 4 orang. Hasil uji Spearman-rho menunjukkan bahwa terdapat korelasi negatif antara TNF-α dan fraksi ejeksi pada pasien gagal jantung kronik di BLU/RSUP Prof. Dr. R. D. Kandou Manado tetapi tidak bermakna secara statistik dengan P = 0,658 (p>0,05). Simpulan: Walaupun terdapat korelasi negatif antara konsengtrasi TNF-α dan fraksi ejeksi pada pasien gagal jantung kronis di BLU/RSUP Prof. Dr. R. D. Kandou Manado, tetapi tidak bermakna secara statistik.Kata kunci: Fraksi Ejeksi Ventrikel Kiri, Gagal Jantung Kronik, TNF-α

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