Abstract Background It has been thought BNP is induced by undetermined stretch-activated receptors, however, which receptor is associated remains unknown. The stretch-activated receptors include mechanically gated channels, which can be activated by a mechanical stimulus alone, and mechanically modulated channels, which require nonmechanical stimuli such as agonists. It has been recently shown that 1.1kb segment of mouse NPPB promoter dose not reproduce the pattern of reactivation of BNP in adult heart, although it could monitor the expression of BNP in neonatal cardiomyocytes. Purpose Our aim is to develop a true BNP reporter mouse and examine whether this mouse is useful or not for the investigation of BNP reactivation mechanism in adult heart and for the measurement of serum-induced BNP expression in patients with heart failure. Methods We generated the BNP reporter mice by knocking luciferase cDNA in the initiation site of NPPB. In vivo imaging of luciferase was performed in the BNP reporter mice after the intraperitoneal injection of luciferin. The luciferase activity was examined in neonatal cardiomyocyte, isolated adult cardiomyocytes, adult cardiac dissected tissue with or without 120–150% stretch or angiotensin II stimulation. Left anterior descending (LAD) coronary artery was ligated to study myocardial infarction. Cardiac dissected tissue segments from the BNP reporter mouse were incubated for 8 hours with 20% serum from patients with or without heart failure and the luciferase activity was measured after homogenization. Results The in vivo imaging system showed the activity of BNP was high in 1 day-old neonates and the reactivation of BNP in the adult heart after LAD ligation could be monitored by the luciferase activity (figure). The treatment of Ang II could increase the activity of pBNP more than ten folds in heart tissue from adult mice. On the other hand, the 120–150% stretch did not show any effect on the activity of pBNP in this system. We could not observe any activation of pBNP in cultured neonatal or adult cardiomyocytes demonstrated by immunostain with antibodies against luciferase after 120–150% stretch. Interestingly, the luciferase activity was extensively higher in cultured heart tissue segments from the BNP reporter mice after the treatment of serum from patients with heart failure than without heart failure. In vivo imaging of BNP reporter mice Conclusion These results indicate the BNP reporter mouse by knock-in technology is useful for the analysis of mechanism in reactivation of BNP in adult heart and the elevation of BNP in patients of heart failure partly due to the serum-derived induction of BNP from heart.
Journal Article Corrected proof Unilateral renal artery spasm complicating hypertensive emergency in a patient with secondary aldosteronism Get access Hiroki Mori, Hiroki Mori Department of Internal Medicine, Owase General Hospital, Owase, Mie, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Ryuji Okamoto, Ryuji Okamoto Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, JapanRegional Medical Support Center, Mie University Hospital, Tsu, Mie, JapanDepartment of Clinical Training and Career Support Center, Mie University Hospital, Tsu, Mie, Japan Corresponding author. E-mail: ryuji@clin.medic.mie-u.ac.jp https://orcid.org/0000-0002-8067-398X Search for other works by this author on: Oxford Academic PubMed Google Scholar Shintaro Sakaguchi, Shintaro Sakaguchi Department of Internal Medicine, Owase General Hospital, Owase, Mie, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Takafumi Koji, Takafumi Koji Department of Internal Medicine, Owase General Hospital, Owase, Mie, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Kaoru Dohi Kaoru Dohi Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan https://orcid.org/0000-0002-5078-6326 Search for other works by this author on: Oxford Academic PubMed Google Scholar European Heart Journal - Cardiovascular Imaging, jeae010, https://doi.org/10.1093/ehjci/jeae010 Published: 11 January 2024 Article history Published: 11 January 2024 Corrected and typeset: 18 January 2024
Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypertension and cardiac hypertrophy. Although it is known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease, the mechanism remains unknown. Here, we review the functions and the roles of BNP in the heart-kidney interaction. In addition, we discuss the relevant molecular mechanisms that suggest BNP is protective against chronic kidney diseases and heart failure, especially in terms of the counterparts of the renin-angiotensin-aldosterone system (RAAS). The renal medulla has been reported to express depressor substances. The extract of the papillary tips from kidneys may induce the expression and secretion of BNP from cardiomyocytes. A better understanding of these processes will help accelerate pharmacological treatments for heart-kidney disease.
We investigated whether the disruption of C-C motif chemokine receptor (CCR) 2 may attenuate the development of pulmonary arterial hypertension (PAH) in any rat models with the reversal of the associated pro-inflammatory state and vascular dysfunction, and synergize with a conventional pulmonary vasodilator.
Introduction: Brain natriuretic peptide (BNP) levels are relatively higher in patients with heart failure with preserved ejection fraction (HFpEF) than heart failure with reduced ejection fraction (HFrEF); however, the mechanism remains unclear. BNP is induced by undetermined stretch-activated receptors including mechanically gated channels, which can be activated by a mechanical stimulus alone, and mechanically modulated channels, which require nonmechanical stimuli such as agonists. Thus it is possible that serum-induced expression of BNP may contribute to the increase of BNP in patients. Purpose: Our purpose is to examine whether serum-induced BNP expression (iBNP) partly contributes to the increase in BNP in patients with HFpEF. Methods: We generated the BNP reporter mice by knocking luciferase cDNA in the initiation site of NPPB . Neonatal cardiomyocytes were isolated and cultured from 2-day-old neonates. These cardiomyocytes were stimulated for 24 hours with 20% serum from patients with HFpEF or HFrEF (n=114 and 82, respectively) and the luciferase activity was examined as iBNP and the ratio of iBNP to BNP was measured. The patients’ characteristics and clinical parameters were compared and multivariate regression analysis was performed using SPSS version 25. Results: The mean ages were 71 yrs in HFpEF and 67 yrs in HFrEF. The female gender was higher in HFpEF (46% vs 32%). The prevalence of atrial fibrillation and hypertension and the use of calcium channel blocker (CCB) were higher in HFpEF than in HFrEF (31 vs 17%, 66 vs 43%, 28 vs 18%). The prevalence of coronary artery disease, chronic kidney disease and diabetes mellitus were lower in HFpEF than HFrEF (21 vs 42%, 44 vs 74%, 25 vs 44%). The ratio of iBNP to BNP was significantly higher in HFpEF than in HFrEF (26.9 vs 16.1, P<0.001). Multivariate regression analysis showed the existence of HFpEF was an independent predictor for the ratio of iBNP to BNP after adjusting all other measurements (β=0.154, P=0.032). Age, hemoglobin, the use of CCB and the deceleration time were also independent predictors (β=0.167, P=0.025; β=0.203, P=0.006; β=0.138, P=0.049; β=0.143, P=0.049, respectively). Conclusions: These results indicate the elevation of BNP in patients with HFpEF is partly due to the iBNP from heart.
Abstract Extent of myocardial fibrosis in hemodialysis patients has been associated with poor prognosis. Myocardial extracellular volume (ECV) quantification using contrast enhanced cardiac computed tomography (CT) is a novel method to determine extent of myocardial fibrosis. Cardiac CT-based myocardial ECV in hemodialysis patients with those of propensity-matched non-hemodialysis control subjects were compared. Twenty hemodialysis patients (mean age, 67.4 ± 9.6 years; 80% male) and 20 propensity-matched non-hemodialysis controls (mean age, 66.3 ± 9.1 years; 85% male) who underwent comprehensive cardiac CT consisted of calcium scoring, coronary CT angiography, stress perfusion CT and delayed enhancement CT were evaluated. Myocardial ECV was significantly greater in the hemodialysis group than in the control group (33.8 ± 4.7% versus 26.6 ± 2.9%; P < 0.0001). In the hemodialysis group, modest correlation was evident between myocardial ECV and left atrial volume index ( r = 0.54; P = 0.01), while there was no correlation between myocardial ECV and other cardiac parameters including left ventricular mass index and severity of myocardial ischemia. Cardiac CT-based myocardial ECV may offer a potential imaging biomarker for myocardial fibrosis in HD patients.
Hypertensive emergency is an important entity which should be managed adequately. A 65-year-old woman presented with blindness and elevated blood pressure of 254/131 mmHg. She was diagnosed with hypertensive emergency on physical examination, and brain magnetic resonance imaging showed posterior reversible encephalopathy syndrome (PRES) with bilateral thalamic haemorrhage. After controlling her blood pressure with intravenous antihypertensive agents, periaortitis and retroperitoneal fibrosis (RPF) were manifested by left hydronephrosis and creatinine elevation. She was diagnosed with periaortitis/RPF. Her blood pressure was well controllable, and PRES improved after treatment with prednisolone. Periaortitis/RPF should not be overlooked when hypertensive emergency suddenly occurs in patients with no history of hypertension.
