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Article: Editorial: Lipids and inflammation in health and disease, volume II.

Bezsonov, Evgeny / Baig, Mirza S / Bukrinsky, Michael / Myasoedova, Veronika / Ravani, Alessio / Sukhorukov, Vasily / Zhang, Dongwei / Khotina, Victoria / Orekhov, Alexander

Frontiers in cardiovascular medicine

2023 Volume 10, Page(s) 1174902

Language	English
Publishing date	2023-04-12
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2023.1174902
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Article ; Online: LDL lowering effect of PCSK9 inhibition is reduced in women.

Myasoedova, Veronika A / Rimbert, Antoine / Camera, Marina / Le May, Cedric / Capoulade, Romain / Cariou, Bertrand / Poggio, Paolo

European heart journal. Cardiovascular pharmacotherapy

2023 Volume 9, Issue 4, Page(s) 337–342

Abstract: Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of plasma low-density lipoprotein cholesterol (LDL-C) concentration, and its inhibition reduces the risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to assess ...

Abstract	Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of plasma low-density lipoprotein cholesterol (LDL-C) concentration, and its inhibition reduces the risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the sex-differential effect of either pharmacological or genetic inhibition of PCSK9 on LDL-C levels. Methods and results: We meta-analyzed six real-life studies (1216 men and 641 women) that investigated the effects of PCSK9 monoclonal antibodies (mAbs) on LDL-C reduction in men and women. Despite higher LDL-C levels in women at baseline [mean difference (MD) = 17.4 mg/dL, P < 0.0001, women = 175 mg/dL vs. men = 152 mg/dL], the LDL-C reduction under PCSK9 mAb treatment was significantly greater in men (MD = 7.6 mg/dL, 95% confidence interval: 2.7-12.4, P = 0.002) than in women.We tested the sex-related association of the loss-of-function variant PCSK9-R46L with LDL-C plasma levels in 382 813 individuals (219 301 women and 163 512 men) free of lipid-lowering drugs from the UK Biobank general population cohort. The magnitude of LDL-C reduction was larger in men than in women (mean LDL-C difference: -35 mg/dL vs. -26 mg/dL, when comparing homozygous carriers with non-carriers in men and women, respectively). The relationship between PCSK9-R46L and LDL-C was significantly dependent on sex (P for interaction = 7.2e-04). Conclusion: These results demonstrate by complementary approaches that the decrease in LDL-C mediated by PCSK9 inhibition is slightly, but significantly, less marked in women than in men. These data reinforce the need for specific studies to develop sex-specific recommendations for the management of ASCVD in women.
MeSH term(s)	Male ; Humans ; Female ; Proprotein Convertase 9/genetics ; Cholesterol, LDL ; Antibodies, Monoclonal/adverse effects ; Hypolipidemic Agents ; Atherosclerosis/diagnosis ; Atherosclerosis/drug therapy ; Atherosclerosis/genetics
Chemical Substances	PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-) ; Cholesterol, LDL ; Antibodies, Monoclonal ; Hypolipidemic Agents
Language	English
Publishing date	2023-02-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2808613-2
ISSN	2055-6845 ; 2055-6837
ISSN (online)	2055-6845
ISSN	2055-6837
DOI	10.1093/ehjcvp/pvad009
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Article ; Online: Non-stenotic fibro-calcific aortic valve as a predictor of myocardial infarction recurrence.

Myasoedova, Veronika A / Chiesa, Mattia / Cosentino, Nicola / Bonomi, Alice / Ludergnani, Monica / Bozzi, Michele / Valerio, Vincenza / Moschetta, Donato / Massaiu, Ilaria / Mantegazza, Valentina / Marenzi, Giancarlo / Poggio, Paolo

European journal of preventive cardiology

2024

Abstract: Background: Patients with acute myocardial infarction (AMI) are at increased risk of recurrent cardiovascular events. Non-stenotic aortic valve fibro-calcific remodeling (AVSc), reflecting systemic damage, may serve as a new marker of risk.: ... ...

Abstract	Background: Patients with acute myocardial infarction (AMI) are at increased risk of recurrent cardiovascular events. Non-stenotic aortic valve fibro-calcific remodeling (AVSc), reflecting systemic damage, may serve as a new marker of risk. Objectives: To stratify subgroups of AMI patients with specific probabilities of recurrent AMI and to evaluate the importance of AVSc in this setting. Methods: Consecutive AMI patients (n = 2530) were admitted at Centro Cardiologico Monzino (2010-2019) and followed up for 5 years. Patients were divided into study (n = 1070) and test (n = 966) cohorts. Topological data analysis (TDA) was used to stratify patient subgroups, while Kaplan-Meier and Cox regressions analyses were used to evaluate the significance of baseline characteristics. Results: TDA identified 11 subgroups of AMI patients with specific baseline characteristics. Two subgroups showed the highest rate of reinfarction after 5 years from the indexed AMI with a combined hazard ratio (HR) of 3.8 (95%CI: 2.7-5.4) compared to the other subgroups. This was confirmed in the test cohort (HR = 3.1; 95%CI: 2.2-4.3). These two subgroups were mostly men, with hypertension and dyslipidemia, who exhibit higher prevalence of AVSc, higher levels of high-sensitive c-reactive protein and creatinine. In the year-by-year analysis, AVSc, adjusted for all confounders, showed an independent association with the increased risk of reinfarction (odds ratio of ∼2 at all time-points), in both the study and the test cohorts (all p < 0.01). Conclusions: AVSc is a crucial variable for identifying AMI patients at high risk of recurrent AMI and its presence should be considered when assessing the management of AMI patients. The inclusion of AVSc in risk stratification models may improve the accuracy of predicting the likelihood of recurrent AMI, leading to more personalized treatment decisions.
Language	English
Publishing date	2024-02-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2626011-6
ISSN	2047-4881 ; 2047-4873
ISSN (online)	2047-4881
ISSN	2047-4873
DOI	10.1093/eurjpc/zwae062
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Article: Red Flags, Prognostic Impact, and Management of Patients With Cardiac Amyloidosis and Aortic Valve Stenosis: A Systematic Review and Meta-Analysis.

Myasoedova, Veronika A / Conte, Maddalena / Valerio, Vincenza / Moschetta, Donato / Massaiu, Ilaria / Petraglia, Laura / Leosco, Dario / Poggio, Paolo / Parisi, Valentina

Frontiers in medicine

2022 Volume 9, Page(s) 858281

Abstract: Background: Cardiac amyloidosis (CA) has been recently recognized as a condition frequently associated with aortic stenosis (AS). The aim of this study was to evaluate: the main characteristics of patients with AS with and without CA, the impact of CA ... ...

Abstract	Background: Cardiac amyloidosis (CA) has been recently recognized as a condition frequently associated with aortic stenosis (AS). The aim of this study was to evaluate: the main characteristics of patients with AS with and without CA, the impact of CA on patients with AS mortality, and the effect of different treatment strategies on outcomes of patients with AS with concomitant CA. Materials and methods: A detailed search related to CA in patients with AS and outcomes was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventeen studies enrolling 1,988 subjects (1,658 AS alone and 330 AS with CA) were included in the qualitative and quantitative analysis of main patients with AS characteristics with and without CA, difference in mortality, and treatment strategy. Results: The prevalence of CA resulted in a mean of 15.4% and it was even higher in patients with AS over 80 years old (18.2%). Patients with the dual diagnosis were more often males, had lower body mass index (BMI), were more prone to have low flow, low gradient with reduced left ventricular ejection fraction AS phenotype, had higher E/A and E/e', and greater interventricular septum hypertrophy. Lower Sokolow-Lyon index, higher QRS duration, higher prevalence of right bundle branch block, higher levels of Conclusion: Results from our meta-analysis suggest that several specific clinical, electrocardiographic, and echocardiographic features can be considered "red flags" of CA in patients with AS. CA negatively affects the outcome of patients with AS. Patients with concomitant CA and AS benefit from SAVR or TAVI.
Language	English
Publishing date	2022-03-09
Publishing country	Switzerland
Document type	Systematic Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.858281
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Article ; Online: Trans-sialidase Associated with Atherosclerosis: Defining the Identity of a Key Enzyme Involved in the Pathology.

Glanz, Victor Y / Myasoedova, Veronika A / Grechko, Andrey V / Orekhov, Alexander N

Current drug targets

2019 Volume 20, Issue 9, Page(s) 938–941

Abstract: Atherosclerosis is associated with the increased trans-sialidase activity, which can be detected in the blood plasma of atherosclerosis patients. The likely involvement in the disease pathogenesis made this activity an interesting research subject and ... ...

Abstract	Atherosclerosis is associated with the increased trans-sialidase activity, which can be detected in the blood plasma of atherosclerosis patients. The likely involvement in the disease pathogenesis made this activity an interesting research subject and the enzyme that may perform such activity was isolated and characterized in terms of substrate specificity and enzymatic properties. It was found that the enzyme has distinct optimum pH values, and its activity was enhanced by the presence of Ca2+ ions. Most importantly, the enzyme was able to cause atherogenic modification of lowdensity lipoprotein (LDL) particles in vitro. However, the identity of the discovered enzyme remained to be defined. Currently, sialyltransferases, mainly ST6Gal I, are regarded as major contributors to sialic acid metabolism in human blood. In this mini-review, we discuss the possibility that atherosclerosis- associated trans-sialidase does, in fact, belong to the sialyltransferases family.
MeSH term(s)	Animals ; Atherosclerosis/enzymology ; Atherosclerosis/metabolism ; Calcium/metabolism ; Humans ; Hydrogen-Ion Concentration ; Lipoproteins, LDL/metabolism ; N-Acetylneuraminic Acid/blood ; Sialyltransferases/blood ; Sialyltransferases/metabolism ; Substrate Specificity
Chemical Substances	Lipoproteins, LDL ; Sialyltransferases (EC 2.4.99.-) ; N-Acetylneuraminic Acid (GZP2782OP0) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2019-04-03
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2064859-5
ISSN	1873-5592 ; 1389-4501
ISSN (online)	1873-5592
ISSN	1389-4501
DOI	10.2174/1389450120666190308111619
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Article ; Online: Sex-Specific Features of Calcific Aortic Valve Disease.

Summerhill, Volha I / Moschetta, Donato / Orekhov, Alexander N / Poggio, Paolo / Myasoedova, Veronika A

International journal of molecular sciences

2020 Volume 21, Issue 16

Abstract: Calcific aortic valve disease (CAVD) is the most common valvular heart disease in developed countries predominantly affecting the elderly population therefore posing a large economic burden. It is a gradually progressive condition ranging from mild valve ...

Abstract	Calcific aortic valve disease (CAVD) is the most common valvular heart disease in developed countries predominantly affecting the elderly population therefore posing a large economic burden. It is a gradually progressive condition ranging from mild valve calcification and thickening, without the hemodynamic obstruction, to severe calcification impairing leaflet motion, known as aortic stenosis (AS). The progression of CAVD occurs over many years, and it is extremely variable among individuals. It is also associated with an increased risk of coronary events and mortality. The recent insights into the CAVD pathophysiology included an important role of sex. Accumulating evidence suggests that, in patients with CAVD, sex can determine important differences in the relationship between valvular calcification process, fibrosis, and aortic stenosis hemodynamic severity between men and women. Consequently, it has implications on the development of different valvular phenotypes, left ventricular hypertrophy, and cardiovascular outcomes in men and women. Along these lines, taking into account the sex-related differences in diagnosis, prognosis, and treatment outcomes is of profound importance. In this review, the sex-related differences in patients with CAVD, in terms of pathobiology, clinical phenotypes, and outcomes were discussed.
MeSH term(s)	Animals ; Aortic Valve/pathology ; Aortic Valve Stenosis/epidemiology ; Aortic Valve Stenosis/pathology ; Calcinosis/epidemiology ; Calcinosis/pathology ; Female ; Humans ; Hypertrophy, Left Ventricular/pathology ; Male ; Phenotype ; Sex Characteristics ; Signal Transduction ; Treatment Outcome
Language	English
Publishing date	2020-08-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21165620
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Article ; Online: The Diabetes Mellitus-Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation.

Poznyak, Anastasia / Grechko, Andrey V / Poggio, Paolo / Myasoedova, Veronika A / Alfieri, Valentina / Orekhov, Alexander N

International journal of molecular sciences

2020 Volume 21, Issue 5

Abstract: Diabetes mellitus comprises a group of carbohydrate metabolism disorders that share a common main feature of chronic hyperglycemia that results from defects of insulin secretion, insulin action, or both. Insulin is an important anabolic hormone, and its ... ...

Abstract	Diabetes mellitus comprises a group of carbohydrate metabolism disorders that share a common main feature of chronic hyperglycemia that results from defects of insulin secretion, insulin action, or both. Insulin is an important anabolic hormone, and its deficiency leads to various metabolic abnormalities in proteins, lipids, and carbohydrates. Atherosclerosis develops as a result of a multistep process ultimately leading to cardiovascular disease associated with high morbidity and mortality. Alteration of lipid metabolism is a risk factor and characteristic feature of atherosclerosis. Possible links between the two chronic disorders depending on altered metabolic pathways have been investigated in numerous studies. It was shown that both types of diabetes mellitus can actually induce atherosclerosis development or further accelerate its progression. Elevated glucose level, dyslipidemia, and other metabolic alterations that accompany the disease development are tightly involved in the pathogenesis of atherosclerosis at almost every step of the atherogenic process. Chronic inflammation is currently considered as one of the key factors in atherosclerosis development and is present starting from the earliest stages of the pathology initiation. It may also be regarded as one of the possible links between atherosclerosis and diabetes mellitus. However, the data available so far do not allow for developing effective anti-inflammatory therapeutic strategies that would stop atherosclerotic lesion progression or induce lesion reduction. In this review, we summarize the main aspects of diabetes mellitus that possibly affect the atherogenic process and its relationship with chronic inflammation. We also discuss the established pathophysiological features that link atherosclerosis and diabetes mellitus, such as oxidative stress, altered protein kinase signaling, and the role of certain miRNA and epigenetic modifications.
MeSH term(s)	Animals ; Atherosclerosis/etiology ; Atherosclerosis/metabolism ; Atherosclerosis/pathology ; Diabetes Mellitus/physiopathology ; Glucose/metabolism ; Humans ; Inflammation/complications ; Insulin Resistance ; Lipids/analysis ; Oxidative Stress
Chemical Substances	Lipids ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2020-03-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21051835
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Article ; Online: Dysregulation of Iron Metabolism-Linked Genes at Myocardial Tissue and Cell Levels in Dilated Cardiomyopathy.

Massaiu, Ilaria / Campodonico, Jeness / Mapelli, Massimo / Salvioni, Elisabetta / Valerio, Vincenza / Moschetta, Donato / Myasoedova, Veronika A / Cappellini, Maria Domenica / Pompilio, Giulio / Poggio, Paolo / Agostoni, Piergiuseppe

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: In heart failure, the biological and clinical connection between abnormal iron homeostasis, myocardial function, and prognosis is known; however, the expression profiles of iron-linked genes both at myocardial tissue and single-cell level are not well ... ...

Abstract	In heart failure, the biological and clinical connection between abnormal iron homeostasis, myocardial function, and prognosis is known; however, the expression profiles of iron-linked genes both at myocardial tissue and single-cell level are not well defined. Through publicly available bulk and single-nucleus RNA sequencing (RNA-seq) datasets of left ventricle samples from adult non-failed (NF) and dilated cardiomyopathy (DCM) subjects, we aim to evaluate the altered iron metabolism in a diseased condition, at the whole cardiac tissue and single-cell level. From the bulk RNA-seq data, we found 223 iron-linked genes expressed at the myocardial tissue level and 44 differentially expressed between DCM and NF subjects. At the single-cell level, at least 18 iron-linked expressed genes were significantly regulated in DCM when compared to NF subjects. Specifically, the iron metabolism in DCM cardiomyocytes is altered at several levels, including: (1) imbalance of Fe
MeSH term(s)	Adult ; Humans ; Cardiomyopathy, Dilated/metabolism ; Myocardium/metabolism ; Down-Regulation ; Myocytes, Cardiac/metabolism ; Heart Failure/metabolism ; 5-Aminolevulinate Synthetase/genetics ; Scavenger Receptors, Class A/genetics
Chemical Substances	ALAS2 protein, human (EC 2.3.1.37) ; 5-Aminolevulinate Synthetase (EC 2.3.1.37) ; SCARA5 protein, human ; Scavenger Receptors, Class A
Language	English
Publishing date	2023-02-02
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/ijms24032887
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Article ; Online: Efficacy of cardiometabolic drugs in reduction of epicardial adipose tissue: a systematic review and meta-analysis.

Myasoedova, Veronika A / Parisi, Valentina / Moschetta, Donato / Valerio, Vincenza / Conte, Maddalena / Massaiu, Ilaria / Bozzi, Michele / Celeste, Fabrizio / Leosco, Dario / Iaccarino, Guido / Genovese, Stefano / Poggio, Paolo

Cardiovascular diabetology

2023 Volume 22, Issue 1, Page(s) 23

Abstract: Background: Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs that already show cardiovascular benefits. The aim of this study is to ... ...

Abstract	Background: Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs that already show cardiovascular benefits. The aim of this study is to evaluate the effect of cardiometabolic drugs on EAT reduction. Methods: A detailed search related to the effect on EAT reduction due to cardiometabolic drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT2-i), and statins was conducted according to PRISMA guidelines. Eighteen studies enrolling 1064 patients were included in the qualitative and quantitative analyses. Results: All three analyzed drug classes, in particular GLP-1 RA, show a significant effect on EAT reduction (GLP-1 RA standardize mean difference (SMD) = - 1.005; p < 0.001; SGLT2-i SMD = - 0.552; p < 0.001, and statin SMD = - 0.195; p < 0.001). The sensitivity analysis showed that cardiometabolic drugs strongly benefit EAT thickness reduction, measured by ultrasound (overall SMD of - 0.663; 95%CI - 0.79, - 0.52; p < 0.001). Meta-regression analysis revealed younger age and higher BMI as significant effect modifiers of the association between cardiometabolic drugs and EAT reduction for both composite effect and effect on EAT thickness, (age Z: 3.99; p < 0.001 and Z: 1.97; p = 0.001, respectively; BMI Z: - 4.40; p < 0.001 and Z: - 2.85; p = 0.004, respectively). Conclusions: Cardiometabolic drugs show a significant beneficial effect on EAT reduction. GLP-1 RA was more effective than SGLT2-i, while statins had a rather mild effect. We believe that the most effective treatment with these drugs should target younger patients with high BMI.
MeSH term(s)	Humans ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/drug therapy ; Cardiovascular Diseases/prevention & control ; Glucagon-Like Peptide 1 ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Obesity ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
Chemical Substances	Glucagon-Like Peptide 1 (89750-14-1) ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Sodium-Glucose Transporter 2 Inhibitors
Language	English
Publishing date	2023-01-31
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	2093769-6
ISSN	1475-2840 ; 1475-2840
ISSN (online)	1475-2840
ISSN	1475-2840
DOI	10.1186/s12933-023-01738-2
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Article: Anti-Inflammation and Anti-Oxidation: The Key to Unlocking the Cardiovascular Potential of SGLT2 Inhibitors and GLP1 Receptor Agonists.

Myasoedova, Veronika A / Bozzi, Michele / Valerio, Vincenza / Moschetta, Donato / Massaiu, Ilaria / Rusconi, Valentina / Di Napoli, Daniele / Ciccarelli, Michele / Parisi, Valentina / Agostoni, Piergiuseppe / Genovese, Stefano / Poggio, Paolo

Antioxidants (Basel, Switzerland)

2023 Volume 13, Issue 1

Abstract: Type 2 diabetes mellitus (T2DM) is a prevalent and complex metabolic disorder associated with various complications, including cardiovascular diseases. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists ( ... ...

Abstract	Type 2 diabetes mellitus (T2DM) is a prevalent and complex metabolic disorder associated with various complications, including cardiovascular diseases. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1-RA) have emerged as novel therapeutic agents for T2DM, primarily aiming to reduce blood glucose levels. However, recent investigations have unveiled their multifaceted effects, extending beyond their glucose-lowering effect. SGLT2i operate by inhibiting the SGLT2 receptor in the kidneys, facilitating the excretion of glucose through urine, leading to reduced blood glucose levels, while GLP1-RA mimic the action of the GLP1 hormone, stimulating glucose-dependent insulin secretion from pancreatic islets. Both SGLT2i and GLP1-RA have shown remarkable benefits in reducing major cardiovascular events in patients with and without T2DM. This comprehensive review explores the expanding horizons of SGLT2i and GLP1-RA in improving cardiovascular health. It delves into the latest research, highlighting the effects of these drugs on heart physiology and metabolism. By elucidating their diverse mechanisms of action and emerging evidence, this review aims to recapitulate the potential of SGLT2i and GLP1-RA as therapeutic options for cardiovascular health beyond their traditional role in managing T2DM.
Language	English
Publishing date	2023-12-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox13010016
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