An Impaired Natriuretic Peptide Hormone System May Play a Role in COVID-19 Severity in Vulnerable Populations

Advanced age, underlying cardiovascular disease (including hypertension), and obesity are associated with a higher risk of progression to severe hypoxemia, acute respiratory distress syndrome (ARDS), and death in COVID-19-infected patients. African Americans have a higher degree of COVID-19 mortality. The incidence of salt-sensitive hypertension is higher in older individuals and African Americans. Lower circulating levels of natriuretic peptides, key regulators of vascular tone and kidney function, have been associated with salt-sensitive hypertension and obesity. Evidence has accumulated that ANP administered to pulmonary endothelial cells, isolated lungs, and patients suffering from ARDS reduces endothelial damage and preserves the endothelial barrier, thereby reducing pulmonary edema and inflammation. Epidemiologic and pharmacologic data suggest that deficiencies in the natriuretic peptide hormone system may contribute to the development of severe lung pathology in COVID-19 patients, and treatments that augment natriuretic peptide signaling may have potential to limit progression to ARDS.

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An impaired natriuretic peptide hormone system may play a role in COVID‐19 severity in vulnerable populations

FASEB BioAdvances ◽

10.1096/fba.2020-00042 ◽

2020 ◽

Vol 2 (10) ◽

pp. 596-599

Author(s):

Mark G. Currie ◽

Daniel P. Zimmer ◽

Perry V. Halushka

Keyword(s):

Natriuretic Peptide ◽

Vulnerable Populations ◽

Peptide Hormone ◽

Hormone System

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Atrial natriuretic peptide levels correlate with salt-sensitive hypertension and volume expansion in African-Americans

American Journal of Hypertension ◽

10.1016/0895-7061(96)81603-7 ◽

1996 ◽

Vol 9 (4) ◽

pp. 50A

Author(s):

H WARD

Keyword(s):

African Americans ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Volume Expansion ◽

Salt Sensitive Hypertension ◽

Atrial Natriuretic

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The small molecule N-Methyl pyrrolidone tunes the natriuretic peptide hormone system into a pro osteogenic state

Bone ◽

10.1016/j.bone.2007.12.149 ◽

2008 ◽

Vol 42 ◽

pp. S80

Author(s):

Grahame McKenzie ◽

Bryn Hardwick ◽

Blanca SanMiguel ◽

Bik Chopra ◽

Giovanna Creasey ◽

...

Keyword(s):

Natriuretic Peptide ◽

Small Molecule ◽

Peptide Hormone ◽

Methyl Pyrrolidone ◽

Hormone System

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Abstract 17240: A Pilot Clinical Trial to Study Racial Differences in Natriuretic Peptide Response to a High-Carbohydrate Challenge

Circulation ◽

10.1161/circ.138.suppl_1.17240 ◽

2018 ◽

Vol 138 (Suppl_1) ◽

Author(s):

Nirav Patel ◽

Griffin Russell ◽

Orlando M Gutierrez ◽

Ganesh Halade ◽

Vasundhara Kain ◽

...

Keyword(s):

Racial Differences ◽

Natriuretic Peptide ◽

Dietary Intervention ◽

Salt Intake ◽

African Ancestry ◽

Venous Blood ◽

Research Unit ◽

Cardiometabolic Disease ◽

Older Individuals ◽

High Carbohydrate

Introduction: Human genetic studies have shown a greater risk of cardiometabolic disease with genetically lower natriuretic peptide (NP) levels. We have previously shown that blacks have lower NP levels than whites albeit in older individuals, which is partly explained by genetic factors. A high-carbohydrate challenge in young healthy whites was associated with a reduction in N-terminal pro atrial NP (NTproANP) levels, but no data exist in blacks. Hypothesis: We hypothesized that 1) the baseline differences in NP levels by race would be evident in young adults with no comorbidities; 2) blacks would have a reduction in NTproANP levels in response to high-carbohydrate challenge similar to whites but the magnitude of change would differ. Methods: Healthy self-identified blacks and whites were screened for the presence of laboratory abnormalities. Each eligible participant was provided 3 days of study diet to standardize salt intake. After the dietary intervention, subjects were brought to the clinical research unit for a high-carbohydrate challenge. Venous blood was collected every hour for 8 hours to perform biochemical assays. African ancestry proportions among self-identified blacks were also determined. Results: We recruited 56 healthy participants with a mean age of 26 years, 48% female, 54% whites, mean body mass index 26 kg/m 2 , and an average proportion of 90% African ancestry among self-identified blacks. We found that BNP levels were 24% (95% CI 53 to 6) and N-terminal-proB-type NP (NTproBNP) levels were 44% (95% CI 99 to 17) lower in blacks compared with whites. The decrease in NTproANP levels in response to carbohydrate challenge differed by race (p for interaction=0.03). In response to a carbohydrate challenge, blacks had a 24% reduction in the NTproANP levels (p=0.01) vs. a 47% decrease in the NTproANP in whites (p<0.001) ( Figure, Panel A ), with no change in NTproBNP levels in both races ( Figure, Panel B ). Conclusions: Blacks have an endogenously suppressed NP system which may be a biologic determinant contributing to racial disparities in cardiometabolic disease. We have shown that high-carbohydrate diet has a differential effect on NP system by race which needs to be considered while individualizing strategies for disease prevention. ( NCT# 03072602 ).

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Association of β-amyloid level, clinical progression and longitudinal cognitive change in normal older individuals

Neurology ◽

10.1212/wnl.0000000000011222 ◽

2020 ◽

pp. 10.1212/WNL.0000000000011222

Author(s):

Laura M. van der Kall ◽

Thanh Truong ◽

Samantha C Burnham ◽

Vincent Doré ◽

Rachel S Mulligan ◽

...

Keyword(s):

Proportional Hazards ◽

Cognitive Change ◽

Cox Proportional Hazards ◽

Imaging Biomarkers ◽

Older Individuals ◽

Mixed Effect ◽

Preclinical Ad ◽

Risk Of Progression ◽

Very High

Objective:To determine the effect of Aβ level on progression risk to MCI or dementia and longitudinal cognitive change in cognitively normal (CN) older individuals.Methods:All CN from the Australian Imaging Biomarkers and Lifestyle study (AIBL) with Aβ PET and ≥3 years follow-up were included (n=534; age 72±6 yrs; 27% Aβ positive; follow-up 5.3±1.7 yrs). Aβ level was divided using the standardised 0-100 Centiloid scale: <15 CL negative, 15-25 CL uncertain, 26-50 CL moderate, 51-100 CL high, >100 CL very high, noting >25 CL approximates a positive scan. Cox proportional hazards analysis and linear mixed effect models were used to assess risk of progression and cognitive decline.Results:Aβ levels in 63% were negative, 10% uncertain, 10% moderate, 14% high and 3% very high. Fifty-seven (11%) progressed to MCI or dementia. Compared to negative Aβ, the hazard ratio for progression for moderate Aβ was 3.2 (95% CI 1.3-7.6; p<0.05), for high was 7.0 (95% CI 3.7-13.3; p<0.001) and for very high was 11.4 (95% CI 5.1-25.8; p<0.001). Decline in cognitive composite score was minimal in the moderate group (-0.02 SD/year, p=0.05) while the high and very high declined substantially (high -0.08 SD/year, p<0.001; very high -0.35 SD/year p<0.001).Conclusion:The risk of MCI or dementia over 5 years in older CN is related to Aβ level on PET, 5% if negative vs 25% if positive but ranging from 12% if 26-50 CL to 28% if 51-100 CL and 50% if >100 CL. This information may be useful for dementia risk counselling and aid design of preclinical AD trials.

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Getting a G–RRP on regulated exocytosis in the heart

The Journal of Cell Biology ◽

10.1083/jcb.200710021 ◽

2007 ◽

Vol 179 (3) ◽

pp. 371-373 ◽

Cited By ~ 1

Author(s):

Christopher C. Glembotski

Keyword(s):

Skeletal Muscle ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Peptide Hormone ◽

Secretory Cells ◽

Related Protein ◽

Atrial Myocytes ◽

Regulated Exocytosis ◽

Regulated Secretion ◽

New Protein

A study by Rybkin et al. (see p. 527) substantially advances our understanding of regulated exocytois by specialized secretory cells, such as atrial myocytes. A second member of the Ras-related protein family, RRP17, was identified and shown to participate in regulating the secretion of the cardiac-derived peptide hormone, atrial natriuretic peptide. In addition to the heart, RRP17 was shown to be expressed in neuronal, pancreatic, and skeletal muscle cells, suggesting a widespread role in regulated secretion for this new protein.

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