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Article ; Online: The Good and the Bad: Immune Cells and Hypertension.

Hay, Meredith

2015 Volume 117, Issue 10, Page(s) 830–831

MeSH term(s)	Animals ; Blood Pressure ; Hypertension/immunology ; Male ; Myeloid Cells/immunology ; Nephritis/immunology
Language	English
Publishing date	2015-10-23
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.115.307506
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Article ; Online: Sex, the brain and hypertension: brain oestrogen receptors and high blood pressure risk factors.

Hay, Meredith

Clinical science (London, England : 1979)

2016 Volume 130, Issue 1, Page(s) 9–18

Abstract: Hypertension is a major contributor to worldwide morbidity and mortality rates related to cardiovascular disease. There are important sex differences in the onset and rate of hypertension in humans. Compared with age-matched men, premenopausal women are ... ...

Abstract	Hypertension is a major contributor to worldwide morbidity and mortality rates related to cardiovascular disease. There are important sex differences in the onset and rate of hypertension in humans. Compared with age-matched men, premenopausal women are less likely to develop hypertension. However, after age 60, the incidence of hypertension increases in women and even surpasses that seen in older men. It is thought that changes in levels of circulating ovarian hormones as women age may be involved in the increase in hypertension in older women. One of the key mechanisms involved in the development of hypertension in both men and women is an increase in sympathetic nerve activity (SNA). Brain regions important for the regulation of SNA, such as the subfornical organ, the paraventricular nucleus and the rostral ventral lateral medulla, also express specific subtypes of oestrogen receptors. Each of these brain regions has also been implicated in mechanisms underlying risk factors for hypertension such as obesity, stress and inflammation. The present review brings together evidence that links actions of oestrogen at these receptors to modulate some of the common brain mechanisms involved in the ability of hypertensive risk factors to increase SNA and blood pressure. Understanding the mechanisms by which oestrogen acts at key sites in the brain for the regulation of SNA is important for the development of novel, sex-specific therapies for treating hypertension.
MeSH term(s)	Age Factors ; Animals ; Blood Pressure ; Brain/metabolism ; Brain/physiopathology ; Comorbidity ; Female ; Health Status Disparities ; Humans ; Hypertension/diagnosis ; Hypertension/epidemiology ; Hypertension/metabolism ; Hypertension/physiopathology ; Inflammation/epidemiology ; Inflammation/metabolism ; Inflammation/physiopathology ; Male ; Middle Aged ; Obesity/epidemiology ; Obesity/metabolism ; Obesity/physiopathology ; Receptors, Estrogen/metabolism ; Risk Factors ; Sex Factors ; Signal Transduction ; Stress, Psychological/epidemiology ; Stress, Psychological/metabolism ; Stress, Psychological/physiopathology ; Sympathetic Nervous System/metabolism ; Sympathetic Nervous System/physiopathology
Chemical Substances	Receptors, Estrogen
Language	English
Publishing date	2016-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	206835-7
ISSN	1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
ISSN (online)	1470-8736
ISSN	0301-0538 ; 0009-0360 ; 0143-5221
DOI	10.1042/CS20150654
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Article ; Online: His and hers hypertension-down to a T?

Hay, Meredith

American journal of physiology. Renal physiology

2015 Volume 308, Issue 8, Page(s) F822–3

MeSH term(s)	Angiotensin II/pharmacology ; Animals ; Humans ; Kidney/drug effects ; Male ; T-Lymphocytes/drug effects
Chemical Substances	Angiotensin II (11128-99-7)
Language	English
Publishing date	2015-04-15
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00667.2014
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Article ; Online: A Year of Challenge and Change.

Samuelson, Linda C / Hay, Meredith / Pollock, Jennifer

Physiology (Bethesda, Md.)

2020 Volume 35, Issue 6, Page(s) 358–360

MeSH term(s)	COVID-19/epidemiology ; COVID-19/virology ; Humans ; Pandemics ; Periodicals as Topic ; Physiology ; SARS-CoV-2/isolation & purification ; Societies, Scientific
Language	English
Publishing date	2020-10-22
Publishing country	United States
Document type	Editorial
ZDB-ID	2158667-6
ISSN	1548-9221 ; 1548-9213
ISSN (online)	1548-9221
ISSN	1548-9213
DOI	10.1152/physiol.00032.2020
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Article ; Online: The genomic basis of sporadic and recurrent pregnancy loss: a comprehensive in-depth analysis of 24,900 miscarriages.

Finley, Jenna / Hay, Sara / Oldzej, Jeannine / Meredith, Matthew M / Dzidic, Natasa / Slim, Rima / Aradhya, Swaroop / Hovanes, Karine / Sahoo, Trilochan

Reproductive biomedicine online

2022 Volume 45, Issue 1, Page(s) 125–134

Abstract: Research question: What is the genetic cause of sporadic and recurrent pregnancy loss and does the frequency and nature of chromosomal abnormalities play a role? Types and frequency of all identifiable chromosomal abnormalities were determined to inform ...

Abstract	Research question: What is the genetic cause of sporadic and recurrent pregnancy loss and does the frequency and nature of chromosomal abnormalities play a role? Types and frequency of all identifiable chromosomal abnormalities were determined to inform our understanding, medical management and recurrence risk for patients experiencing pregnancy loss. Design: Genome-wide single-nucleotide polymorphism-based chromosomal microarray (SNP-CMA) were used to evaluate 24,900 products of conception samples from various forms of pregnancy losses. Results: Sporadic miscarriage (64.7%) or recurrent pregnancy loss (RPL) (22%) were the most common referrals. Clinically significant abnormalities were observed in 55.8% (13,910) of samples, variants of uncertain significance in 1.8%, and normal results in 42.4%. In addition to autosomal trisomies (in 36% of samples), polyploidy and large segmental imbalances were identified in 7.8% and 2.8% of samples, respectively. Analysis of sequential samples from 1103 patients who had experienced RPL provided important insight into possible predispositions to RPL. Conclusions: This expansive chromosomal microarray analyses of pregnancy loss samples illuminates our understanding of the full spectrum, relative frequencies and the role of genomic abnormalities in pregnancy loss. The empiric observations described here provide useful insight for clinicians and highlight the importance of high-resolution genomic testing for comprehensive evaluation and risk assessment of individuals experiencing pregnancy loss.
MeSH term(s)	Abortion, Habitual/genetics ; Abortion, Induced ; Chromosome Aberrations ; Female ; Genetic Testing ; Genomics ; Humans ; Pregnancy
Language	English
Publishing date	2022-03-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2113823-0
ISSN	1472-6491 ; 1472-6483
ISSN (online)	1472-6491
ISSN	1472-6483
DOI	10.1016/j.rbmo.2022.03.014
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Article ; Online: Glycopeptide drugs: A pharmacological dimension between "Small Molecules" and "Biologics".

Apostol, Christopher R / Hay, Meredith / Polt, Robin

Peptides

2020 Volume 131, Page(s) 170369

Abstract: Peptides are an important class of molecules with diverse biological activities. Many endogenous peptides, especially neuropeptides and peptide hormones, play critical roles in development and regulating homeostasis. Furthermore, as drug candidates their ...

Abstract	Peptides are an important class of molecules with diverse biological activities. Many endogenous peptides, especially neuropeptides and peptide hormones, play critical roles in development and regulating homeostasis. Furthermore, as drug candidates their high receptor selectivity and potent binding leads to reduced off-target interactions and potential negative side effects. However, the therapeutic potential of peptides is severely hampered by their poor stability in vivo and low permeability across biological membranes. Several strategies have been successfully employed over the decades to address these concerns, and one of the most promising strategies is glycosylation. It has been demonstrated in numerous cases that glycosylation is an effective synthetic approach to improve the pharmacokinetic profiles and membrane permeability of peptides. The effects of glycosylation on peptide stability and peptide-membrane interactions in the context of blood-brain barrier penetration will be explored. Numerous examples of glycosylated analogues of endogenous peptides targeting class A and B G-protein coupled receptors (GPCRs) with an emphasis on O-linked glycopeptides will be reviewed. Notable examples of N-, S-, and C-linked glycopeptides will also be discussed. A small section is devoted to synthetic methods for the preparation of glycopeptides and requisite amino acid glycoside building blocks.
MeSH term(s)	Amino Acid Sequence ; Amino Acids ; Biological Products/isolation & purification ; Biological Products/metabolism ; Biological Products/pharmacology ; Blood-Brain Barrier/drug effects ; Blood-Brain Barrier/metabolism ; Central Nervous System/drug effects ; Central Nervous System/metabolism ; Chemistry Techniques, Synthetic ; Glycopeptides/chemical synthesis ; Glycopeptides/classification ; Glycopeptides/metabolism ; Glycopeptides/pharmacology ; Glycosides/chemistry ; Glycosides/metabolism ; Glycosylation ; Humans ; Opioid Peptides/chemical synthesis ; Opioid Peptides/metabolism ; Opioid Peptides/pharmacology ; Protein Stability ; Proteolysis ; Receptors, G-Protein-Coupled/agonists ; Receptors, G-Protein-Coupled/antagonists & inhibitors ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism
Chemical Substances	Amino Acids ; Biological Products ; Glycopeptides ; Glycosides ; Opioid Peptides ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2020-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	769028-9
ISSN	1873-5169 ; 0196-9781
ISSN (online)	1873-5169
ISSN	0196-9781
DOI	10.1016/j.peptides.2020.170369
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Article: Glycosylated Ang-(1-7) MasR Agonist Peptide Poly Lactic-co-Glycolic Acid (PLGA) Nanoparticles and Microparticles in Cognitive Impairment: Design, Particle Preparation, Physicochemical Characterization, and In Vitro Release.

Encinas-Basurto, David / Konhilas, John P / Polt, Robin / Hay, Meredith / Mansour, Heidi M

Pharmaceutics

2022 Volume 14, Issue 3

Abstract: Heart failure (HF) causes decreased brain perfusion in older adults, and increased brain and systemic inflammation increases the risk of cognitive impairment and Alzheimer’s disease (AD). Glycosylated Ang-(1-7) MasR agonists (PNA5) has shown improved ... ...

Abstract	Heart failure (HF) causes decreased brain perfusion in older adults, and increased brain and systemic inflammation increases the risk of cognitive impairment and Alzheimer’s disease (AD). Glycosylated Ang-(1-7) MasR agonists (PNA5) has shown improved bioavailability, stability, and brain penetration compared to Ang-(1-7) native peptide. Despite promising results and numerous potential applications, clinical applications of PNA5 glycopeptide are limited by its short half-life, and frequent injections are required to ensure adequate treatment for cognitive impairment. Therefore, sustained-release injectable formulations of PNA5 glycopeptide are needed to improve its bioavailability, protect the peptide from degradation, and provide sustained drug release over a prolonged time to reduce injection administration frequency. Two types of poly(D,L-lactic-co-glycolic acid) (PLGA) were used in the synthesis to produce nanoparticles (≈0.769−0.35 µm) and microparticles (≈3.7−2.4 µm) loaded with PNA5 (ester and acid-end capped). Comprehensive physicochemical characterization including scanning electron microscopy, thermal analysis, molecular fingerprinting spectroscopy, particle sizing, drug loading, encapsulation efficiency, and in vitro drug release were conducted. The data shows that despite the differences in the size of the particles, sustained release of PNA5 was successfully achieved using PLGA R503H polymer with high drug loading (% DL) and high encapsulation efficiency (% EE) of >8% and >40%, respectively. While using the ester-end PLGA, NPs showed poor sustained release as after 72 h, nearly 100% of the peptide was released. Also, lower % EE and % DL values were observed (10.8 and 3.4, respectively). This is the first systematic and comprehensive study to report on the successful design, particle synthesis, physicochemical characterization, and in vitro glycopeptide drug release of PNA5 in PLGA nanoparticles and microparticles.
Language	English
Publishing date	2022-03-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14030587
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Article ; Online: PNA6, a Lactosyl Analogue of Angiotensin-(1-7), Reverses Pain Induced in Murine Models of Inflammation, Chemotherapy-Induced Peripheral Neuropathy, and Metastatic Bone Disease.

Sulaiman, Maha I / Alabsi, Wafaa / Szabo, Lajos / Hay, Meredith / Polt, Robin / Largent-Milnes, Tally M / Vanderah, Todd W

International journal of molecular sciences

2023 Volume 24, Issue 19

Abstract: Pain is the most significant impairment and debilitating challenge for patients with bone metastasis. Therefore, the primary objective of current therapy is to mitigate and prevent the persistence of pain. Thus, cancer-induced bone pain is described as a ...

Abstract	Pain is the most significant impairment and debilitating challenge for patients with bone metastasis. Therefore, the primary objective of current therapy is to mitigate and prevent the persistence of pain. Thus, cancer-induced bone pain is described as a multifaceted form of discomfort encompassing both inflammatory and neuropathic elements. We have developed a novel non-addictive pain therapeutic, PNA6, that is a derivative of the peptide Angiotensin-(1-7) and binds the Mas receptor to decrease inflammation-related cancer pain. In the present study, we provide evidence that PNA6 attenuates inflammatory, chemotherapy-induced peripheral neuropathy (CIPN) and cancer pain confined to the long bones, exhibiting longer-lasting efficacious therapeutic effects. PNA6, Asp-Arg-Val-Tyr-Ile-His-Ser-(O-β-Lact)-amide, was successfully synthesized using solid phase peptide synthesis (SPPS). PNA6 significantly reversed inflammatory pain induced by 2% carrageenan in mice. A second murine model of platinum drug-induced painful peripheral neuropathy was established using oxaliplatin. Mice in the oxaliplatin-vehicle treatment groups demonstrated significant mechanical allodynia compared to the oxaliplatin-PNA6 treatment group mice. In a third study modeling a complex pain state, E0771 breast adenocarcinoma cells were implanted into the femur of female C57BL/6J wild-type mice to induce cancer-induced bone pain (CIBP). Both acute and chronic dosing of PNA6 significantly reduced the spontaneous pain behaviors associated with CIBP. These data suggest that PNA6 is a viable lead candidate for treating chronic inflammatory and complex neuropathic pain.
MeSH term(s)	Humans ; Mice ; Female ; Animals ; Oxaliplatin/adverse effects ; Cancer Pain/drug therapy ; Disease Models, Animal ; Mice, Inbred C57BL ; Neuralgia/chemically induced ; Neuralgia/drug therapy ; Neuralgia/complications ; Hyperalgesia/chemically induced ; Hyperalgesia/drug therapy ; Hyperalgesia/complications ; Breast Neoplasms/drug therapy ; Bone Neoplasms/complications ; Bone Neoplasms/drug therapy ; Antineoplastic Agents/adverse effects
Chemical Substances	Oxaliplatin (04ZR38536J) ; angiotensin I (1-7) (IJ3FUK8MOF) ; Antineoplastic Agents
Language	English
Publishing date	2023-10-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241915007
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Article ; Online: APS: Moving Forward to Aid Our Membership.

Sands, Jeff M / Hay, Meredith / Brown, Dennis

Physiology (Bethesda, Md.)

2018 Volume 33, Issue 6, Page(s) 370–371

MeSH term(s)	Committee Membership ; Humans ; Physiology/organization & administration ; Societies, Scientific/organization & administration ; Surveys and Questionnaires
Language	English
Publishing date	2018-10-10
Publishing country	United States
Document type	Editorial
ZDB-ID	2158667-6
ISSN	1548-9221 ; 1548-9213
ISSN (online)	1548-9221
ISSN	1548-9213
DOI	10.1152/physiol.00039.2018
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Article ; Online: Hypertension and Age-Related Cognitive Impairment: Common Risk Factors and a Role for Precision Aging.

Hay, Meredith / Barnes, Carol / Huentelman, Matt / Brinton, Roberta / Ryan, Lee

Current hypertension reports

2020 Volume 22, Issue 10, Page(s) 80

Abstract: Purpose of review: Precision Aging® is a novel concept that we have recently employed to describe how the model of precision medicine can be used to understand and define the multivariate risks that drive age-related cognitive impairment (ARCI). ... ...

Abstract	Purpose of review: Precision Aging® is a novel concept that we have recently employed to describe how the model of precision medicine can be used to understand and define the multivariate risks that drive age-related cognitive impairment (ARCI). Hypertension and cardiovascular disease are key risk factors for both brain function and cognitive aging. In this review, we will discuss the common mechanisms underlying the risk factors for both hypertension and ARCI and how the convergence of these mechanisms may be amplified in an individual to drive changes in brain health and accelerate cognitive decline. Recent findings: Currently, our cognitive health span does not match our life span. Age-related cognitive impairment and preventing and treating ARCI will require an in-depth understanding of the interrelated risk factors, including individual genetic profiles, that affect brain health and brain aging. Hypertension and cardiovascular disease are important risk factors for ARCI. And, many of the risk factors for developing hypertension, such as diabetes, smoking, stress, viral infection, and age, are shared with the development of ARCI. We must first understand the mechanisms common to the converging risk factors in hypertension and ARCI and then design person-specific therapies to optimize individual brain health. The understanding of the convergence of shared risk factors between hypertension and ARCI is required to develop individualized interventions to optimize brain health across the life span. We will conclude with a discussion of possible steps that may be taken to decrease ARCI and optimize an individual's cognitive life span.
MeSH term(s)	Aging ; Brain/physiopathology ; Cognitive Dysfunction ; Humans ; Hypertension/complications ; Precision Medicine ; Risk Factors
Keywords	covid19
Language	English
Publishing date	2020-09-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-020-01090-w
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