Prognostic Value of Urinary and Plasma C-Type Natriuretic Peptide in Acute Decompensated Heart Failure

Ma, Xiao; Chen, Yang; Reginauld, Shawn; Scott, Christopher G.; Iyer, Seethalakshmi; Schaefer, Jacob J.; Ichiki, Tomoko; Chen, Horng H.; Rule, Andrew D.; Burnett, John C.; Sangaralingham, S. Jeson

doi:10.1016/j.jchf.2021.04.013

Cited by 7 publications

(7 citation statements)

References 37 publications

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“…While conventionally CNP has not been considered an important HF biomarker, Ma et al . 73 measured NT-proBNP and plasma and urinary CNP in healthy subjects and in patients with ADHF. They reported significantly elevated concentrations of urinary and plasma CNP in ADHF patients compared with healthy subjects.…”

Section: Differential Regulation Of Anp and Bnp In Heart Failure And ...mentioning

confidence: 99%

Natriuretic peptide pathways in heart failure: further therapeutic possibilities

Sangaralingham

Kühn

Cannone

et al. 2022

Cardiovascular Research

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The discovery of the heart as an endocrine organ resulted in a remarkable recognition of the natriuretic peptide system (NPS). Specifically, research has established the production of atrial (ANP) and B-type natriuretic peptides (BNP) from the heart, which exert pleiotropic cardiovascular, endocrine, renal, and metabolic actions via the particulate guanylyl cyclase A receptor (GC-A) and the second messenger, cGMP. C-type natriuretic peptide (CNP) is produced in the endothelium and kidney and mediates important protective auto/paracrine actions via GC-B and cGMP. These actions, in part, participate in the efficacy of sacubitril/valsartan in heart failure (HF) due to augmentation of the NPS. Here we will review important insights into the biology of the NPS, the role of precision medicine and focus on the phenotypes of human genetic variants of ANP and BNP in the general population and the relevance to HF. We will also provide an update of the existence of NP deficiency states, including in HF, which provide the rationale for further therapeutics for the NPS. Finally, we will review the field of peptide engineering and the development of novel designer NPs for the treatment of HF. Notably, the recent discovery of a first-in-class small molecule GC-A enhancer, which is orally deliverable, will be highlighted. These innovative designer NPs and small molecule possess enhanced and novel properties for the treatment of HF and cardiovascular diseases.

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Section: Differential Regulation Of Anp and Bnp In Heart Failure And ...mentioning

confidence: 99%

Natriuretic peptide pathways in heart failure: further therapeutic possibilities

Sangaralingham

Kühn

Cannone

et al. 2022

Cardiovascular Research

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“…128 healthy subjects (71% are female) were recruited from the Mayo Clinic Biobank (MCB) as we have previously described [11]. The MCB is a comprehensive and ongoing registry for collecting biological samples including blood from volunteers to aid ongoing population studies which focus on precision medicine, medical diagnostics, and therapeutics.…”

Section: Study Populationmentioning

confidence: 99%

“…The natriuretic peptide system (NPS) serves a fundamental role in controlling blood pressure (BP), volume homeostasis, and the functional and structural adaptation of the heart and kidneys to physiologic or pathophysiologic stresses [1][2][3][4][5][6]. To date, the family of human natriuretic peptides (NPs) includes the cardiac-derived hormones atrial natriuretic peptide (ANP) and b-type natriuretic peptide (BNP), and the renovascular-derived hormone c-type natriuretic peptide (CNP) [7][8][9][10][11]. In response to hypertension-induced cardiovascular (CV) remodeling or diseases such as heart failure (HF), diabetes, and chronic kidney disease (CKD), production of all three peptides can up-regulate to exert pluripotent beneficial actions including vasodilatation, diuresis, natriuresis, prevention of myocardial hypertrophy, and suppression of cardiac and renal fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Evidence for Angiotensin II as a Naturally Existing Suppressor for the Guanylyl Cyclase A Receptor and Cyclic GMP Generation

Iyer

et al. 2023

IJMS

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The natriuretic peptide system (NPS) and renin-angiotensin-aldosterone system (RAAS) function oppositely at multiple levels. While it has long been suspected that angiotensin II (ANGII) may directly suppress NPS activity, no clear evidence to date supports this notion. This study was designed to systematically investigate ANGII–NPS interaction in humans, in vivo, and in vitro. Circulating atrial, b-type, and c-type natriuretic peptides (ANP, BNP, CNP), cyclic guanosine monophosphate (cGMP), and ANGII were simultaneously investigated in 128 human subjects. Prompted hypothesis was validated in vivo to determine the influence of ANGII on ANP actions. The underlying mechanisms were further explored via in vitro approaches. In humans, ANGII demonstrated an inverse relationship with ANP, BNP, and cGMP. In regression models predicting cGMP, adding ANGII levels and the interaction term between ANGII and natriuretic peptides increased the predictive accuracy of the base models constructed with either ANP or BNP, but not CNP. Importantly, stratified correlation analysis further revealed a positive association between cGMP and ANP or BNP only in subjects with low, but not high, ANGII levels. In rats, co-infusion of ANGII even at a physiological dose attenuated cGMP generation mediated by ANP infusion. In vitro, we found the suppressive effect of ANGII on ANP-stimulated cGMP requires the presence of ANGII type-1 (AT1) receptor and mechanistically involves protein kinase C (PKC), as this suppression can be substantially rescued by either valsartan (AT1 blocker) or Go6983 (PKC inhibitor). Using surface plasmon resonance (SPR), we showed ANGII has low binding affinity to the guanylyl cyclase A (GC-A) receptor compared to ANP or BNP. Our study reveals ANGII is a natural suppressor for the cGMP-generating action of GC-A via AT1/PKC dependent manner and highlights the importance of dual-targeting RAAS and NPS in maximizing beneficial properties of natriuretic peptides in cardiovascular protection.

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“…There was no cross-reactivity with ANP or CNP in this assay. Plasma CNP was measured with a non-equilibrium radioimmunoassay kit (Phoenix Pharmaceutical, Burlingame, CA) using an antibody against human CNP as previously reported (11). The range of the standard curve used in the assay was 0.5 to 128 pg, with the lowest detection of 0.5 pg.…”

Section: Biomarker Measurements In Human Plasmamentioning

confidence: 99%

“…The natriuretic peptide system (NPS) serves a fundamental role in controlling blood pressure (BP), volume homeostasis, and the functional and structural adaptation of the heart and kidneys to physiologic or pathophysiologic stresses (1)(2)(3)(4)(5)(6). To date, the family of human natriuretic peptides (NPs) includes the cardiac-derived hormones atrial natriuretic peptide (ANP) and b-type natriuretic peptide (BNP), and the renovascularderived hormone c-type natriuretic peptide (CNP) (7)(8)(9)(10)(11). In response to hypertensioninduced cardiovascular remodeling or diseases such as heart failure (HF), diabetes, and chronic kidney disease (CKD), production of all three peptides can up-regulate to exert pluripotent beneficial actions including vasodilatation, diuresis, natriuresis, prevention of myocardial hypertrophy, and suppression of cardiac and renal fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Evidence for Angiotensin Ii as a Naturally Existing Suppressor for the Natriuretic Peptide System

Iyer

et al. 2023

Preprint

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Background: Natriuretic peptide system (NPS) and renin angiotensin aldosterone system (RAAS) function oppositely at multiple levels. While it has long been suspected that angiotensin II (ANGII) may directly suppress NPS activity, no clear evidence to date support this notion. Objectives: This study was designed to systematically investigate ANGII-NPS interaction in humans, in vivo, and in vitro for translational insights. Methods: Circulating atrial, b-type, and c-type natriuretic peptides (ANP, BNP, CNP), cyclic guanosine monophosphate (cGMP), and ANGII were simultaneously investigated in 128 human subjects. Prompted hypothesis was validated in rat model to determine influence of ANGII on ANP actions. Multiple engineered HEK293 cells and surface plasmon resonance (SPR) technology were leveraged for mechanistic exploration. Results: In humans, ANGII showed inverse relationship with ANP, BNP, and cGMP. In regression models predicting cGMP, adding ANGII levels and interaction term between ANGII and natriuretic peptide increased predicting accuracy of base models constructed with either ANP or BNP, but not CNP. Importantly, stratified correlation analysis further revealed positive association between cGMP with ANP or BNP only in subjects with low, but not high, ANGII levels. In rats, co-infusion of ANGII even at physiological dose attenuated blood pressure reduction and cGMP generation triggered by ANP infusion. In vitro, we showed that the suppression effect of ANGII on ANP-stimulated cGMP requires the presence of ANGII type-1 (AT1) receptor and mechanistically involves protein kinase C (PKC), which can be substantially rescued by either valsartan (AT1 blocker) or Go6983 (PKC inhibitor). Using SPR, we showed ANGII has low affinity for particulate guanylyl cyclase A (GC-A) receptor binding compared to ANP or BNP. Conclusions: Our study reveals ANGII as a natural suppressor for cGMP-generating action of GC-A via AT1/PKC dependent manner and highlights importance of dual-targeting RAAS and NPS in maximizing beneficial properties of natriuretic peptides in cardiovascular disease.

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Prognostic Value of Urinary and Plasma C-Type Natriuretic Peptide in Acute Decompensated Heart Failure

Cited by 7 publications

References 37 publications

Natriuretic peptide pathways in heart failure: further therapeutic possibilities

Natriuretic peptide pathways in heart failure: further therapeutic possibilities

Evidence for Angiotensin II as a Naturally Existing Suppressor for the Guanylyl Cyclase A Receptor and Cyclic GMP Generation

Evidence for Angiotensin Ii as a Naturally Existing Suppressor for the Natriuretic Peptide System

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