Abstract 383: Heart-Kidney: Myocardial Infarction Mediates Renal Fibrosis and Activates Renal Molecular Remodeling in the Absence of Heart Failure

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Fernando L Martin ◽  
Brenda K Huntley ◽  
Gerald E Harders ◽  
Sharon M Sandberg ◽  
Horng H Chen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Renal Function ◽  
Microarray Analysis ◽  
Structural Changes ◽  
Cell Communication ◽  
Kidney Cortex ◽  
Water Excretion ◽  
Mild Reduction ◽  
Poor Outcomes

Background : Studies in human myocardial infarction (MI) suggest that even in the absence of heart failure (HF) alterations in renal function may occur and contribute to poor outcomes. After MI a decline in renal function may be seen acutely by mechanisms which are unclear. The long term consequences of MI upon renal function and structure remain poorly defined. We hypothesized that even without pre-existing renal disease, renal functional and structural changes would be present following MI. Methods : Cardiorenal function and structure were assessed in Wistar rats, Sham (S; n=10) and MI groups (n=9) 3 weeks after MI. GFR was determined by inulin clearance. Blood was obtained for PRA and aldosterone. Hearts and kidneys were harvested for histological analysis. Cardiac function was assessed by echo. Genome-wide microarray analysis was performed on kidney cortex (KC) and medulla (KM) (Affymetrix GeneChip® Rat Genome 230 2.0). Results : EF decreased after MI (S:62.8±2.3, MI:42.8±6.5 %, p<0.01) and LVEDd increased (p<0.005) PRA and aldosterone activation were absent. Blood pressure (BP) was not different between groups. There was no HF as sodium and water excretion was maintained. GFR tended to decrease (S:2.9±0.3, MI:2.4±0.2 ml/min, NS). Picrosirius Red staining for collagen in the KC and KM after MI showed greater fibrosis especially in the RM (KC S:1.1±0.2, MI:3.5±0.6 %, p<0.001 and KM S:1±0.2, MI:18.8±6 %, p<0.005). Microarray analysis revealed that 303 genes significantly changed in KM and 407 genes in the KC after MI (1.5 fold, P<0.05). Gene dysregulation was related to cell proliferation, metabolic processes and cell communication (Z value>2). Conclusion : We conclude that experimental MI results in renal structural remodeling characterized by renal cortical and medullary fibrosis with a mild reduction in GFR and extensive modulation of molecular pathways related to renal growth and metabolism. This investigation provides evidence for a heart-kidney connection after MI by mechanisms which remain to be defined. We also conclude that therapies for MI targeting the heart also should be evaluated for properties of renoprotection.

Myocardial infarction impairs renal function, induces renal interstitial fibrosis, and increases renal KIM-1 expression: implications for cardiorenal syndrome

2012 ◽  
Vol 302 (9) ◽  
pp. H1884-H1893 ◽  
Author(s):  
Suree Lekawanvijit ◽  
Andrew R. Kompa ◽  
Yuan Zhang ◽  
Bing H. Wang ◽  
Darren J. Kelly ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Renal Function ◽  
Body Weight ◽  
Structural Changes ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Systolic Function ◽  
Kidney Cortex ◽  
Positive Staining ◽  
Time Points

Progressive decline in renal function coexists with myocardial infarction (MI); however, little is known about its pathophysiology. This study aimed to systematically identify post-MI renal changes (functional, histological, and molecular) over time in a rat MI model and examine potential mechanisms that may underlie these changes. Rats were randomized into three groups: nonoperated, sham, and MI. Cardiac and renal function was assessed before death at 1, 4, 8, 12, and 16 wk with tissues collected for histological, protein, and gene studies. Tail-cuff blood pressure was lower in MI than sham and nonoperated animals only at 1 wk ( P < 0.05). Systolic function was reduced ( P < 0.0001) while heart/body weight and left ventricle/body weight were significantly greater in MI animals at all time points. Glomerular filtration rate decreased following MI at 1 and 4 wk ( P < 0.05) but not at 8 and 12 wk and then deteriorated further at 16 wk ( P = 0.052). Increased IL-6 gene and transforming growth factor (TGF)-β protein expression as well as macrophage infiltration in kidney cortex was detected at 1 wk ( P < 0.05). Renal cortical interstitial fibrosis was significantly greater in MI animals from 4 wk, while TGF-β bioactivity (phospho-Smad2) was upregulated at all time points. The degree of fibrosis increased and was maximal at 16 wk. In addition, kidney injury molecule-1-positive staining in the tubules was more prominent in MI animals, maximal at 1 wk. In conclusion, renal impairment occurs early post-MI and is associated with hemodynamic and structural changes in the kidney possibly via activation of the Smad2 signaling pathway.

Highlighting Exosomes' Function in Cardiovascular Diseases

2021 ◽  
Vol 17 ◽  
Author(s):  
Sidhi Laksono ◽  
Budhi Setianto ◽  
Ananta Siddhi Prawara ◽  
Bambang Dwiputra
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Heart Disease ◽  
Cardiovascular Diseases ◽  
Prognostic Marker ◽  
Therapeutic Agent ◽  
Diagnostic Marker ◽  
Cell Communication ◽  
Surface Protein ◽  
Cardiovascular Patients

: Exosomes as one of the extracellular vesicles’ subgroups played an important role in the cell to cell communication. The cargos and surface protein of exosomes have been known to affect the cardiovascular system both positively and negatively in chronic heart failure, ischemic heart disease, and atherosclerosis. There have been several exosomes that emerged as a potential diagnostic and prognostic marker in cardiovascular patients. However, the conditions affecting the patients and the method of isolation should be considered to create a standardized normal value of the exosomes and the components. CPC-derived exosomes, ADSCs-derived exosomes, and telocyte-derived exosomes have been proven to be capable ofacting as a therapeutic agent in myocardial infarction models. Exosomes have the potential to become a diagnostic marker, prognostic marker, and therapeutic agent in cardiovascular diseases.

scholarly journals Impact of Renal Disease on Natriuretic Peptide Testing for Diagnosing Decompensated Heart Failure and Predicting Mortality

2007 ◽  
Vol 53 (8) ◽  
pp. 1511-1519 ◽  
Author(s):  
Christopher R deFilippi ◽  
Stephen L Seliger ◽  
Susan Maynard ◽  
Robert H Christenson
Keyword(s):  
Heart Failure ◽  
Renal Function ◽  
Natriuretic Peptide ◽  
Estimated Glomerular Filtration Rate ◽  
Area Under The Curve ◽  
Decompensated Heart Failure ◽  
Multivariate Regression Analysis ◽  
Poor Outcomes ◽  
One Year ◽  
Roc Area

Abstract Background: Concomitant occurrence of kidney disease (KD) and heart failure (HF) is common and associated with poor outcomes. Natriuretic peptide studies have typically excluded many individuals with KD. We compared the accuracy of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) for diagnosing decompensated HF and predicting mortality across the spectrum of renal function. Methods: BNP and NT-proBNP were prospectively measured in a cohort of 831 dyspnea patients. KD was defined as an estimated glomerular filtration rate &lt;60 mL · min−1 · (1.73 m2)−1. The accuracy and predictive value of each test for diagnosing decompensated HF and predicting all-cause 1-year mortality were assessed by ROC area under the curve (AUC) and multivariate regression analysis. Results: Among the 831 dyspnea patients, 393 (47%) had KD. The diagnostic accuracies of BNP and NT-proBNP in detecting decompensated HF were similar to each other in patients without KD (AUC 0.75 vs 0.74, respectively; P = 0.60) and in patients with KD (AUC 0.68 vs 0.66; P = 0.10). One-year mortality rates were 36.3% and 19.0% in those with and without KD, respectively (P &lt;0.001). Progressively higher BNP and NT-proBNP concentrations remained predictive of increased mortality in KD patients. Compared with the lowest quartile, quartile 4 of BNP had an adjusted hazards ratio (HR) of 2.6 (95% CI 1.4–4.8; P = 0.004 for trend) and NT-proBNP quartile 4 had an HR of 4.5 (95% CI 2.0–10.2; P &lt;0.001 for trend). Only NT-proBNP remained a predictor of death after adjustment for clinical confounders and the other natriuretic peptide marker. Conclusions: NT-proBNP and BNP are equivalent predictors of decompensated HF across a spectrum of renal function, but NT-proBNP is a superior predictor of mortality.

Low-dose nesiritide improves renal function in heart failure patients following acute myocardial infarction

2010 ◽  
Vol 25 (2) ◽  
pp. 97-103 ◽  
Author(s):  
Qiang Zhao ◽  
Tong-Guo Wu ◽  
Yi Lin ◽  
Biao Li ◽  
Jing-Yun Luo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Renal Function ◽  
Low Dose ◽  
Heart Failure Patients

scholarly journals Expression of B2 Receptor on Circulating CD34-Positive Cells and Outcomes of Myocardial Infarction

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Cong Fu ◽  
Yuhan Cao ◽  
Yuyu Yao ◽  
Shengxing Tang ◽  
Qun Fan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Confidence Interval ◽  
Hazard Ratio ◽  
Cell Surface Receptor ◽  
Kaplan Meier ◽  
Surface Receptor ◽  
Poor Outcomes ◽  
Low Expression

Background. Bradykinin B2 receptor (B2R) is a widely expressed cell surface receptor. The relationship between B2R expression on circulating CD34+ cells and prognosis of myocardial infarction remains unknown.Methods. We analyzed the expression of B2R on circulating CD34-positive cells and plasma VEGF concentration in 174 myocardial infarction patients. All involved patients were divided into two groups: high B2R group and low B2R group according to the median B2R expression percentage. 48 months of follow-up was performed. The endpoints were heart failure and revascularization.Results. The plasma level of VEGF in the low B2R group is67±12 pg/mL, whereas the high B2R group has significantly elevated VEGF levels of145±27 pg/mL(P<0.001). The concentration of VEGF has correlated with expression of B2R (r=0.574,P<0.001). During the 48 months of follow-up, low expression of B2 receptor on circulating CD34-positive cells indicates the high incidence of heart failure (hazard ratio: 2.247; 95% confidence interval: 1.110-4.547;P=0.024) and revascularization (hazard ratio: 2.335; 95% confidence interval: 1.075-5.074;P=0.032). Kaplan-Meier survival analysis showed that the cumulative hazard of heart failure (P=0.014) and revascularization (P=0.032) has significant differences between low B2R and high B2R.Conclusion. Low expression of B2R on circulating progenitor cells indicated the poor outcomes of myocardial infarction.

P4552The prognostic impact of worsening and improved renal function in acute decompensated heart failure with and without plasma volume expansion

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Kawai ◽  
T Yamada ◽  
T Morita ◽  
Y Furukawa ◽  
S Tamaki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Renal Function ◽  
Body Weight ◽  
Plasma Volume ◽  
Acute Decompensated Heart Failure ◽  
The Other ◽  
Prognostic Impact ◽  
Plasma Volume Expansion ◽  
Other Hand ◽  
Poor Outcomes

Abstract Background Recent studies showed that both worsening renal function (WRF) and improved renal function (IRF) during hospitalization are associated with poor prognosis in patients with acute decompensate heart failure (ADHF). On the other hand, plasma volume (PV) expansion plays an essential role in ADHF. However, there is little information about the difference of prognostic impact of WRF and IRF in ADHF patients, relating to PV status (PVS). Methods We prospectively studied 348 patients admitted for ADHF. PVS was defined as follows: actual PV = (1 - hematocrit) × [a + (b × body weight)] (a=1530 in males and a=864 in females, b=41.0 in males and b=47.9 in females); ideal PV = c × body weight (c=39 in males and c=40 in females); and PVS = [(actual PV - ideal PV)/ideal PV] × 100 (%). WRF and IRF were defined as an increase and a decrease in serum creatinine of ≥0.3 mg/dl from admission to discharge, respectively. The endpoint was readmission for worsening heart failure (WHF) within 1 year. Result Median PVS was 6.7% (IQR: −4.1%–16.7%). 43 and 21 patients had WHF in groups with high PVS (PVS ≥ median) and low PVS (PVS > median), respectively. In high PVS group, multivariate Cox analysis showed that IRF was independently and significantly associated with WHF (p=0.016, HR: 2.4 [1.2–4.8]), but WRF was not (p=0.55, HR: 0.7 [0.3–2.1]). On the other hand, in low PVS group, WRF was independently associated with WHF (p=0.035, HR: 3.0 [1.1–8.1]), but IRF was not (p=0.27, HR: 2.1 [0.6–8.0]). Kaplan-Meier analysis revealed that only patients with IRF had a significantly higher risk of WHF than those with stable renal function (SRF) in high PVS group, while patients with WRF had a significantly higher risk of WHF than those with SRF in low PVS group. Worsening heart failure-free rate curves Conclusion In ADHF patients with PV expansion, IRF during hospitalization could predict poor outcomes, but WRF could not. On the other hand, in ADHF patients without PV expansion, not IRF but WRF could predict poor outcomes. PVS guided-therapy may be considered in secondary prevention for WHF.

Abstract 4328: Integrated Network and Microarray Analysis to Identify New Biomarkers of Heart Failure after Myocardial Infarction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Yvan Devaux ◽  
Céline Yvorra ◽  
Mélanie Vausort ◽  
Céline Jeanty ◽  
Francisco Azuaje ◽  
...  
Keyword(s):  
Gene Expression ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Growth Factor ◽  
Microarray Analysis ◽  
Prediction Models ◽  
Differentially Expressed ◽  
Reference Database ◽  
Ppi Network ◽  
New Biomarkers

Purpose : A significant proportion of acute myocardial infarction (MI) patients develop heart failure (HF). Early identification of patients at risk of developing HF after MI would be a major breakthrough. An approach combining the power of biological information networks and the precision of microarray analysis was undertaken to identify new biomarkers of HF. Methods : Since angiogenesis may be related to MI and HF, a protein-protein interaction (PPI) network was constructed by first extracting from the Entrez-Gene database a set of genes relevant to angiogenesis and MI. These genes were used as inputs to retrieve annotated interactions from the Human Protein Reference Database. Potential biomarkers were identified by network analysis. Gene expression profiles of blood cells taken at the time of MI in two groups of 16 patients (high ejection fraction (EF) at 1 month, EF≥45% and low EF at 1 month, EF≤40%) were obtained using oligonucleotide microarrays containing 25,000 genes and compared by Statistical Analysis of Microarrays (SAM). Prediction models based on machine learning were used to classify low and high EF patients. Results : SAM identified 525 genes differentially expressed between patients with high and low EF (fold-change ≥1.3). The PPI network included 556 nodes (proteins) and 686 edges (interactions). A network clustering algorithm identified 53 proteins highly specialized in growth and regulation processes. Out of these, 38 were found differentially expressed by SAM. Further filtering reported 3 genes as the optimal biomarker set: Vascular Endothelial Growth Factor B (VEGFB), Placental Growth Factor (PGF), both pro-angiogenic, and the anti-angiogenic protein Thrombospondin-1 (THBS1). Prediction models reported areas under the receiver operating characteristic curve (AUC) of 0.82 for this biomarker set. Conclusion : The classification performances achieved with the 3 biomarkers stresses the prognostic value of genes involved in angiogenesis. The network-based approach allowed us to identify powerful biomarkers, which could not be identified by applying standard gene expression data analysis only. Therefore, combined network and microarray analysis allows a systematic and less biased approach to biomarker discovery.

Distinct roles for renal particulate and soluble guanylyl cyclases in preserving renal function in experimental acute heart failure

2007 ◽  
Vol 293 (4) ◽  
pp. R1580-R1585 ◽  
Author(s):  
Fernando L. Martin ◽  
Thanom Supaporn ◽  
Horng H. Chen ◽  
Sharon M. Sandberg ◽  
Yuzuru Matsuda ◽  
...  
Keyword(s):  
Heart Failure ◽  
Renal Function ◽  
Acute Heart Failure ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Sodium Reabsorption ◽  
Therapeutic Implications ◽  
Anesthetized Dogs ◽  
Rapid Ventricular Pacing ◽  
Poor Outcomes

Worsening renal function in the setting of human acute heart failure (AHF) predicts poor outcomes, such as rehospitalization and increased mortality. Understanding potential renoprotective mechanisms is warranted. The guanylate cyclase (GC) enzymes and their second messenger cGMP are the target of two important circulating neurohumoral systems with renoprotective properties. Specifically, natriuretic peptides (NP) released from the heart with AHF target particulate GC in the kidney, while the nitric oxide (NO) system is an activator of renal soluble GC. We hypothesized that both systems are essential to preserve renal excretory and hemodynamic function in AHF but with distinct roles. We investigated these roles in three groups of anesthetized dogs (6 each) with AHF induced by rapid ventricular pacing. After a baseline AHF clearance, each group received intrarenal vehicle (control), NG-monomethyl-l-arginine (l-NMMA), a competitive NO inhibitor (50 μg·kg−1·min−1) or a specific NP receptor antagonist, HS-142-1 (0.5 mg/kg). We observed that intrarenal l-NMMA decreased renal blood flow (RBF) without significant decreases in glomerular filtration rate (GFR), urinary sodium excretion (UNaV), or urinary cGMP. In contrast, HS-142-1 resulted in a decrease in UNaV and cGMP excretion together with a reduction in GFR and an increase in distal fractional tubular sodium reabsorption. We conclude that in AHF, the NP system plays a role in maintaining sodium excretion and GFR, while the function of NO is in the maintenance of RBF. These studies have both physiological and therapeutic implications warranting further research into cardiorenal interactions in this syndrome of AHF.

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