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Article: Obesity-associated cardiometabolic complications in polycystic ovary syndrome: The potential role of sodium-glucose cotransporter-2 inhibitors.

Pruett, Jacob E / Romero, Damian G / Yanes Cardozo, Licy L

2023 Volume 14, Page(s) 951099

Abstract: Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is characterized by androgen excess, oligo/anovulation, and polycystic appearance of the ovaries. Women with PCOS have an increased prevalence of ... ...

Abstract	Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is characterized by androgen excess, oligo/anovulation, and polycystic appearance of the ovaries. Women with PCOS have an increased prevalence of multiple cardiovascular risk factors such as insulin resistance, hypertension, renal injury, and obesity. Unfortunately, there is a lack of effective, evidence-based pharmacotherapeutics to target these cardiometabolic complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors provide cardiovascular protection in patients with and without type 2 diabetes mellitus. Although the exact mechanisms of how SGLT2 inhibitors confer cardiovascular protection remains unclear, numerous mechanistic hypotheses for this protection include modulation of the renin-angiotensin system and/or the sympathetic nervous system and improvement in mitochondrial function. Data from recent clinical trials and basic research show a potential role for SGLT2 inhibitors in treating obesity-associated cardiometabolic complications in PCOS. This narrative review discusses the mechanisms of the beneficial effect of SGLT2 inhibitors in cardiometabolic diseases in PCOS.
MeSH term(s)	Female ; Humans ; Diabetes Mellitus, Type 2 ; Hypertension ; Obesity ; Polycystic Ovary Syndrome/drug therapy ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
Chemical Substances	Sodium-Glucose Transporter 2 Inhibitors
Language	English
Publishing date	2023-02-15
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.951099
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Novel biomarkers of childhood and adolescent obesity.

Yanes Cardozo, Licy L / Romero, Damian G

Hypertension research : official journal of the Japanese Society of Hypertension

2021 Volume 44, Issue 8, Page(s) 1030–1033

MeSH term(s)	Adolescent ; Biomarkers ; Body Mass Index ; Humans ; Pediatric Obesity
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-04-14
Publishing country	England
Document type	Editorial
ZDB-ID	1175297-x
ISSN	1348-4214 ; 0916-9636
ISSN (online)	1348-4214
ISSN	0916-9636
DOI	10.1038/s41440-021-00651-z
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Zs.A 3898: Show issues

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Article ; Online: Cardiovascular Events in Polycystic Ovary Syndrome: Is the Debate Settled for Good?

Romero, Damian G / Yanes Cardozo, Licy L

The Journal of clinical endocrinology and metabolism

2021 Volume 106, Issue 12, Page(s) e5258–e5259

MeSH term(s)	Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/etiology ; Female ; Humans ; Polycystic Ovary Syndrome/complications ; Polycystic Ovary Syndrome/epidemiology ; Risk Factors
Language	English
Publishing date	2021-07-09
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	3029-6
ISSN	1945-7197 ; 0021-972X
ISSN (online)	1945-7197
ISSN	0021-972X
DOI	10.1210/clinem/dgab509
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Uh III Zs.134: Show issues

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Article ; Online: Insights Into the Cardiomodulatory Effects of Sex Hormones: Implications in Transgender Care.

Shawky, Noha M / Reckelhoff, Jane F / Alexander, Barbara T / Yanes Cardozo, Licy L

Hypertension (Dallas, Tex. : 1979)

2023 Volume 80, Issue 9, Page(s) 1810–1820

Abstract: Transgender individuals that undergo gender-affirming hormone therapy may experience discrimination in the health care setting with a lack of access to medical personnel competent in transgender medicine. Recent evidence suggests that gender-affirming ... ...

Abstract	Transgender individuals that undergo gender-affirming hormone therapy may experience discrimination in the health care setting with a lack of access to medical personnel competent in transgender medicine. Recent evidence suggests that gender-affirming hormone therapy is associated with an increased risk of cardiovascular diseases and cardiovascular risk factors. A recent statement from the American Heart Association reinforces the importance of cardiovascular-focused clinical management and the necessity for more research into the impact of gender-affirming hormone therapy. With this in mind, this review will highlight the known cardiovascular risk factors associated with gender-affirming hormone therapy and identify potential molecular mechanisms determined from the limited animal studies that explore the role of cross-sex steroids on cardiovascular risk. The lack of data in this understudied population requires future clinical and basic research studies to inform and educate clinicians and their transgender patient population to promote precision medicine for their care to improve their quality of life.
MeSH term(s)	Humans ; Transgender Persons ; Quality of Life ; Gonadal Steroid Hormones ; Transsexualism/therapy ; Cardiovascular Diseases/epidemiology ; Hormones
Chemical Substances	Gonadal Steroid Hormones ; Hormones
Language	English
Publishing date	2023-07-18
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	423736-5
ISSN	1524-4563 ; 0194-911X ; 0362-4323
ISSN (online)	1524-4563
ISSN	0194-911X ; 0362-4323
DOI	10.1161/HYPERTENSIONAHA.123.19501
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Zs.A 1488: Show issues

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Article ; Online: Management of cardiometabolic complications in polycystic ovary syndrome: Unmet needs.

Yanes Cardozo, Licy L / Romero, Damian G

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2021 Volume 35, Issue 11, Page(s) e21945

Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder and the most common cause of androgen excess in reproductive-age women. The heterogeneity of the clinical presentation in PCOS patients suggests the involvement of multiples abnormal ... ...

Abstract	Polycystic ovary syndrome (PCOS) is the most common endocrine disorder and the most common cause of androgen excess in reproductive-age women. The heterogeneity of the clinical presentation in PCOS patients suggests the involvement of multiples abnormal physiological pathways. In addition, women with PCOS have a high prevalence of cardiometabolic risk factors. Unfortunately, limited effective evidence-based therapeutic agents are available to treat the cardiometabolic complications in PCOS patients. Insights from recent studies highlight the multiple opportunities to deliver timely effective medical care for women with PCOS. This perspective manuscript aims to highlight the unmet need for effective and safe management of the cardiometabolic complications in PCOS patients.
MeSH term(s)	Androgen Antagonists/therapeutic use ; Androgens/metabolism ; Contraceptives, Oral/therapeutic use ; Diabetes Mellitus, Type 2/diet therapy ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/etiology ; Dyslipidemias/diet therapy ; Dyslipidemias/drug therapy ; Dyslipidemias/etiology ; Female ; Healthy Lifestyle ; Humans ; Hypertension/diet therapy ; Hypertension/drug therapy ; Hypertension/etiology ; Hypoglycemic Agents/therapeutic use ; Insulin Resistance ; Obesity/diet therapy ; Obesity/drug therapy ; Obesity/etiology ; Obesity/surgery ; Polycystic Ovary Syndrome/complications ; Polycystic Ovary Syndrome/metabolism ; Treatment Outcome
Chemical Substances	Androgen Antagonists ; Androgens ; Contraceptives, Oral ; Hypoglycemic Agents
Language	English
Publishing date	2021-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202002526RR
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Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 296: Show issues

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Article ; Online: Polycystic Ovary Syndrome: Insights from Preclinical Research.

Reckelhoff, Jane F / Shawky, Noha M / Romero, Damian G / Yanes Cardozo, Licy L

Kidney360

2022 Volume 3, Issue 8, Page(s) 1449–1457

Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, affecting approximately 10%. PCOS is diagnosed by the presence of at least two of these three criteria: hyperandrogenemia, oligo- or anovulation, and ... ...

Abstract	Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, affecting approximately 10%. PCOS is diagnosed by the presence of at least two of these three criteria: hyperandrogenemia, oligo- or anovulation, and polycystic ovaries. The most common type (80%) of PCOS includes hyperandrogenemia. PCOS is also characterized by obesity or overweight (in 80% of US women with PCOS), insulin resistance with elevated plasma insulin but not necessarily hyperglycemia, dyslipidemia, proteinuria, and elevated BP. Although elevated compared with age-matched controls, BP may not reach levels considered treatable according to the current clinical hypertension guidelines. However, it is well known that elevated BP, even modestly so, increases the risk of cardiovascular disease. We have developed a model of hyperandrogenemia in rodents that mimics the characteristics of PCOS in women, with increases in body weight, insulin resistance, dyslipidemia, andproteinuria and elevated BP. This review discusses potential mechanisms responsible for the elevated BP in the adult and aging PCOS rat model that may be extrapolated to women with PCOS
MeSH term(s)	Animals ; Anovulation ; Female ; Humans ; Hyperandrogenism/diagnosis ; Insulin Resistance ; Insulins ; Polycystic Ovary Syndrome/diagnosis ; Rats
Chemical Substances	Insulins
Language	English
Publishing date	2022-06-17
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2641-7650
ISSN (online)	2641-7650
DOI	10.34067/KID.0002052022
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Article ; Online: Sodium-Glucose Cotransporter-2 Inhibition Benefits in Cardiorenal Risk in Men and Women.

Pruett, Jacob E / Lirette, Seth T / Romero, Damian G / Yanes Cardozo, Licy L

Journal of the Endocrine Society

2022 Volume 7, Issue 2, Page(s) bvac191

Abstract: Introduction: In addition to their antihyperglycemic action, sodium-glucose cotransporter-2 (SGLT2) inhibitors are used in patients with type 2 diabetes due to their cardioprotective effects. Meta-analyses of large clinical trials have reported mixed ... ...

Abstract	Introduction: In addition to their antihyperglycemic action, sodium-glucose cotransporter-2 (SGLT2) inhibitors are used in patients with type 2 diabetes due to their cardioprotective effects. Meta-analyses of large clinical trials have reported mixed results when examining sex differences in their cardioprotective effects. For example, some studies reported that, compared to women, men had a greater reduction in cardiovascular risk with SGLT2 inhibition. Taking advantage of several recently completed large-scale randomized controlled clinical trials, we tested the hypothesis that women have an attenuated response in primary cardiorenal outcomes to SGLT2 inhibition compared to men. Methods: We performed a systematic search using PubMed and the Cochrane Library to find completed large-scale, prospective, randomized controlled Phase III clinical trials with primary outcomes testing cardiovascular or renal benefit. Studies had to include at least 1000 participants and report data about sex differences in their primary cardiovascular or renal outcomes. Results: The present meta-analysis confirmed that SGLT2 inhibition decreased adverse cardiorenal outcomes in a pooled sex analysis using 13 large-scale clinical trials. SGLT2 inhibition exhibited similar reduction in hazard ratios for both men (0.79, 95% CI, 0.73-0.85) and women (0.78, 95% CI, 0.72-0.84) for adverse cardiorenal outcomes. Conclusion: In contrast to previous findings, our updated meta-analysis suggests that women and men experience similar cardiorenal benefit in response to SGLT2 inhibition. These findings strongly suggest that SGLT2 inhibition therapy should be considered in patients with high risk for cardiovascular disease irrespective of the patient sex.
Language	English
Publishing date	2022-12-13
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvac191
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Article ; Online: Loss of microRNA-21 protects against acetaminophen-induced hepatotoxicity in mice.

Huffman, Alexandra M / Syed, Maryam / Rezq, Samar / Anderson, Christopher D / Yanes Cardozo, Licy L / Romero, Damian G

Archives of toxicology

2023 Volume 97, Issue 7, Page(s) 1907–1925

Abstract: Acetaminophen (APAP)-induced Acute Liver Failure (ALF) is recognized as the most common cause of ALF in Western societies. APAP-induced ALF is characterized by coagulopathy, hepatic encephalopathy, multi-organ failure, and death. MicroRNAs are small, non- ...

Abstract	Acetaminophen (APAP)-induced Acute Liver Failure (ALF) is recognized as the most common cause of ALF in Western societies. APAP-induced ALF is characterized by coagulopathy, hepatic encephalopathy, multi-organ failure, and death. MicroRNAs are small, non-coding RNAs that regulate gene expression at the post-transcriptional level. MicroRNA-21 (miR-21) is dynamically expressed in the liver and is involved in the pathophysiology of both acute and chronic liver injury models. We hypothesize that miR-21genetic ablation attenuates hepatotoxicity following acetaminophen intoxication. Eight-week old miR-21knockout (miR21KO) or wild-type (WT) C57BL/6N male mice were injected with acetaminophen (APAP, 300 mg/kg BW) or saline. Mice were sacrificed 6 or 24 h post-injection. MiR21KO mice presented attenuation of liver enzymes ALT, AST, LDH compared with WT mice 24 h post-APAP treatment. Moreover, miR21KO mice had decreased hepatic DNA fragmentation and necrosis than WT mice after 24 h of APAP treatment. APAP-treated miR21KO mice showed increased levels of cell cycle regulators CYCLIN D1 and PCNA, increased autophagy markers expression (Map1LC3a, Sqstm1) and protein (LC3AB II/I, p62), and an attenuation of the APAP-induced hypofibrinolytic state via (PAI-1) compared with WT mice 24 post-APAP treatment. MiR-21 inhibition could be a novel therapeutic approach to mitigate APAP-induced hepatotoxicity and enhance survival during the regenerative phase, particularly to alter regeneration, autophagy, and fibrinolysis. Specifically, miR-21 inhibition could be particularly useful when APAP intoxication is detected at its late stages and the only available therapy is minimally effective.
MeSH term(s)	Animals ; Male ; Mice ; Acetaminophen/toxicity ; Chemical and Drug Induced Liver Injury/genetics ; Chemical and Drug Induced Liver Injury/prevention & control ; Liver ; Liver Failure, Acute ; Mice, Inbred C57BL ; MicroRNAs/genetics ; MicroRNAs/metabolism
Chemical Substances	Acetaminophen (362O9ITL9D) ; MicroRNAs ; MIRN21 microRNA, mouse
Language	English
Publishing date	2023-05-14
Publishing country	Germany
Document type	Journal Article
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-023-03499-z
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Uf I Zs.90: Show issues

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Article ; Online: Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet: Implications for Polycystic Ovary Syndrome and COVID-19.

Rezq, Samar / Huffman, Alexandra M / Basnet, Jelina / Yanes Cardozo, Licy L / Romero, Damian G

International journal of molecular sciences

2021 Volume 22, Issue 18

Abstract: ... TMPRSS2, TMPRSS4, furin, cathepsin L, and ADAM17) and androgen receptor (AR) expression, in a peripubertal ... cathepsin L were upregulated by DHT and differentially modulated by the diet. DHT upregulated urinary ACE2 ... with Ace2, Tmprss2, furin, cathepsin L, and ADAM17. Our findings suggest that women with PCOS could be ...

Abstract	The susceptibility and the severity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with hyperandrogenism, obesity, and preexisting pulmonary, metabolic, renal, and cardiac conditions. Polycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with obesity, hyperandrogenism, and cardiometabolic dysregulations. We analyzed cardiac, renal, circulatory, and urinary SARS-CoV-2 viral entry proteins (ACE2, TMPRSS2, TMPRSS4, furin, cathepsin L, and ADAM17) and androgen receptor (AR) expression, in a peripubertal androgen exposure model of PCOS. Peripubertal female mice were treated with dihydrotestosterone (DHT) and low (LFD) or high (HFD) fat diet for 90 days. HFD exacerbated DHT-induced increase in body weight, fat mass, and cardiac and renal hypertrophy. In the heart, DHT upregulated AR protein in both LFD and HFD, ACE2 in HFD, and ADAM17 in LFD. In the kidney, AR protein expression was upregulated by both DHT and HFD. Moreover, ACE2 and ADAM17 were upregulated by DHT in both diets. Renal TMPRSS2, furin, and cathepsin L were upregulated by DHT and differentially modulated by the diet. DHT upregulated urinary ACE2 in both diets, while neither treatment modified serum ACE2. Renal AR mRNA expression positively correlated with Ace2, Tmprss2, furin, cathepsin L, and ADAM17. Our findings suggest that women with PCOS could be a population with a high risk of COVID-19-associated cardiac and renal complications. Furthermore, our study suggests that weight loss by lifestyle modifications (i.e., diet) could potentially mitigate COVID-19-associated deleterious cardiorenal outcomes in women with PCOS.
MeSH term(s)	Animals ; COVID-19/immunology ; COVID-19/virology ; Female ; Heart ; Kidney ; Mice ; Mice, Inbred C57BL ; Obesity/immunology ; Obesity/virology ; Polycystic Ovary Syndrome/virology ; Receptors, Coronavirus/immunology ; SARS-CoV-2/physiology ; Virus Internalization
Chemical Substances	Receptors, Coronavirus
Language	English
Publishing date	2021-09-09
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/ijms22189746
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Article ; Online: Cardiac and Renal SARS-CoV-2 Viral Entry Protein Regulation by Androgens and Diet

Samar Rezq / Alexandra M. Huffman / Jelina Basnet / Licy L. Yanes Cardozo / Damian G. Romero

International Journal of Molecular Sciences, Vol 22, Iss 9746, p

Implications for Polycystic Ovary Syndrome and COVID-19

2021 Volume 9746

Abstract	The susceptibility and the severity of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with hyperandrogenism, obesity, and preexisting pulmonary, metabolic, renal, and cardiac conditions. Polycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with obesity, hyperandrogenism, and cardiometabolic dysregulations. We analyzed cardiac, renal, circulatory, and urinary SARS-CoV-2 viral entry proteins (ACE2, TMPRSS2, TMPRSS4, furin, cathepsin L, and ADAM17) and androgen receptor (AR) expression, in a peripubertal androgen exposure model of PCOS. Peripubertal female mice were treated with dihydrotestosterone (DHT) and low (LFD) or high (HFD) fat diet for 90 days. HFD exacerbated DHT-induced increase in body weight, fat mass, and cardiac and renal hypertrophy. In the heart, DHT upregulated AR protein in both LFD and HFD, ACE2 in HFD, and ADAM17 in LFD. In the kidney, AR protein expression was upregulated by both DHT and HFD. Moreover, ACE2 and ADAM17 were upregulated by DHT in both diets. Renal TMPRSS2, furin, and cathepsin L were upregulated by DHT and differentially modulated by the diet. DHT upregulated urinary ACE2 in both diets, while neither treatment modified serum ACE2. Renal AR mRNA expression positively correlated with Ace2, Tmprss2, furin, cathepsin L, and ADAM17. Our findings suggest that women with PCOS could be a population with a high risk of COVID-19-associated cardiac and renal complications. Furthermore, our study suggests that weight loss by lifestyle modifications (i.e., diet) could potentially mitigate COVID-19-associated deleterious cardiorenal outcomes in women with PCOS.
Keywords	polycystic ovary syndrome ; COVID-19 ; SARS-CoV-2 ; angiotensin converting enzyme 2 ; androgens ; obesity ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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