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Article ; Online: Comment on Huh et al. Remnant Cholesterol Is an Independent Predictor of Type 2 Diabetes: A Nationwide Population-Based Cohort Study. Diabetes Care 2023;46:305-312.

Canyelles, Marina / Blanco-Vaca, Francisco / Pérez, Antonio / Escolà-Gil, Joan Carles

2023 Volume 46, Issue 10, Page(s) e203

MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/epidemiology ; Cohort Studies
Language	English
Publishing date	2023-09-18
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc23-0774
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Article ; Online: Gut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease?

Canyelles, Marina / Borràs, Carla / Rotllan, Noemí / Tondo, Mireia / Escolà-Gil, Joan Carles / Blanco-Vaca, Francisco

International journal of molecular sciences

2023 Volume 24, Issue 3

Abstract: Trimethylamine-N-oxide (TMAO) is the main diet-induced metabolite produced by the gut microbiota, and it is mainly eliminated through renal excretion. TMAO has been correlated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) and ... ...

Abstract	Trimethylamine-N-oxide (TMAO) is the main diet-induced metabolite produced by the gut microbiota, and it is mainly eliminated through renal excretion. TMAO has been correlated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) and related complications, such as cardiovascular mortality or major adverse cardiovascular events (MACE). Meta-analyses have postulated that high circulating TMAO levels are associated with an increased risk of cardiovascular events and all-cause mortality, but the link between TMAO and CVD remains not fully consistent. The results of prospective studies vary depending on the target population and the outcome studied, and the adjustment for renal function tends to decrease or reverse the significant association between TMAO and the outcome studied, strongly suggesting that the association is substantially mediated by renal function. Importantly, one Mendelian randomization study did not find a significant association between genetically predicted higher TMAO levels and cardiometabolic disease, but another found a positive causal relationship between TMAO levels and systolic blood pressure, which-at least in part-could explain the link with renal function. The mechanisms by which TMAO can increase this risk are not clearly elucidated, but current evidence indicates that TMAO induces cholesterol metabolism alterations, inflammation, endothelial dysfunction, and platelet activation. Overall, there is no fully conclusive evidence that TMAO is a causal factor of ASCVD, and, especially, whether TMAO induces or just is a marker of hypertension and renal dysfunction requires further study.
MeSH term(s)	Humans ; Gastrointestinal Microbiome/physiology ; Cardiovascular Diseases/chemically induced ; Prospective Studies ; Atherosclerosis/metabolism ; Methylamines/metabolism
Chemical Substances	trimethyloxamine (FLD0K1SJ1A) ; Methylamines
Language	English
Publishing date	2023-01-18
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/ijms24031940
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Article ; Online: FTY720-P, a Biased S1PR Ligand, Increases Mitochondrial Function through STAT3 Activation in Cardiac Cells.

Muñoz, Juan Pablo / Sànchez-Fernàndez-de-Landa, Paula / Diarte-Añazco, Elena María Goretti / Zorzano, Antonio / Blanco-Vaca, Francisco / Julve, Josep

International journal of molecular sciences

2023 Volume 24, Issue 8

Abstract: FTY720 is an FDA-approved sphingosine derivative drug for the treatment of multiple sclerosis. This compound blocks lymphocyte egress from lymphoid organs and autoimmunity through sphingosine 1-phosphate (S1P) receptor blockage. Drug repurposing of ... ...

Abstract	FTY720 is an FDA-approved sphingosine derivative drug for the treatment of multiple sclerosis. This compound blocks lymphocyte egress from lymphoid organs and autoimmunity through sphingosine 1-phosphate (S1P) receptor blockage. Drug repurposing of FTY720 has revealed improvements in glucose metabolism and metabolic diseases. Studies also demonstrate that preconditioning with this compound preserves the ATP levels during cardiac ischemia in rats. The molecular mechanisms by which FTY720 promotes metabolism are not well understood. Here, we demonstrate that nanomolar concentrations of the phosphorylated form of FTY720 (FTY720-P), the active ligand of S1P receptor (S1PR), activates mitochondrial respiration and the mitochondrial ATP production rate in AC16 human cardiomyocyte cells. Additionally, FTY720-P increases the number of mitochondrial nucleoids, promotes mitochondrial morphology alterations, and induces activation of STAT3, a transcription factor that promotes mitochondrial function. Notably, the effect of FTY720-P on mitochondrial function was suppressed in the presence of a STAT3 inhibitor. In summary, our results suggest that FTY720 promotes the activation of mitochondrial function, in part, through a STAT3 action.
MeSH term(s)	Rats ; Humans ; Animals ; Sphingosine ; Fingolimod Hydrochloride/pharmacology ; Propylene Glycols/pharmacology ; Ligands ; Receptors, Lysosphingolipid/metabolism ; Sphingosine-1-Phosphate Receptors/metabolism ; Mitochondria/metabolism ; Adenosine Triphosphate ; Immunosuppressive Agents/pharmacology ; STAT3 Transcription Factor/metabolism
Chemical Substances	FTY 720P ; Sphingosine (NGZ37HRE42) ; Fingolimod Hydrochloride (G926EC510T) ; Propylene Glycols ; Ligands ; Receptors, Lysosphingolipid ; Sphingosine-1-Phosphate Receptors ; Adenosine Triphosphate (8L70Q75FXE) ; Immunosuppressive Agents ; STAT3 protein, human ; STAT3 Transcription Factor
Language	English
Publishing date	2023-04-17
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/ijms24087374
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Article ; Online: PCSK9 plasma concentration is associated with epicardial adipose tissue volume and metabolic control in patients with type 1 diabetes.

Sardà, Helena / Colom, Cristina / Benitez, Sonia / Carreras, Gemma / Amigó, Judit / Miñambres, Inka / Viladés, David / Blanco-Vaca, Francisco / Sanchez-Quesada, Jose Luís / Pérez, Antonio

Scientific reports

2024 Volume 14, Issue 1, Page(s) 7195

Abstract: Patients with type 1 diabetes (T1D) have a greater risk of cardiovascular disease. Proconvertase subtilisin-kexin 9 (PCSK9) is involved in the atherosclerosis process. This study aimed to determine the relationship between PCSK9 levels and epicardial ... ...

Abstract	Patients with type 1 diabetes (T1D) have a greater risk of cardiovascular disease. Proconvertase subtilisin-kexin 9 (PCSK9) is involved in the atherosclerosis process. This study aimed to determine the relationship between PCSK9 levels and epicardial adipose tissue (EAT) volume and cardiometabolic variables in patients with T1D. This was an observational cross-sectional study including 73 patients with T1D. Clinical, biochemical and imaging data were collected. We divided the patients into two groups according to their glycemic control and the EAT index (iEAT) percentile. We performed a correlation analysis between the collected variables and PCSK9 levels; subsequently, we performed a multiple regression analysis with the significant parameters. The mean age was 47.6 ± 8.5 years, 58.9% were men, and the BMI was 26.9 ± 4.6 kg/m
MeSH term(s)	Male ; Humans ; Adult ; Middle Aged ; Female ; Diabetes Mellitus, Type 1/metabolism ; Proprotein Convertase 9/metabolism ; Epicardial Adipose Tissue ; Glycated Hemoglobin ; Subtilisin ; Cross-Sectional Studies ; Dyslipidemias ; Adipose Tissue/metabolism
Chemical Substances	PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-) ; Glycated Hemoglobin ; Subtilisin (EC 3.4.21.62)
Language	English
Publishing date	2024-03-26
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-57708-5
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Article ; Online: (r)HDL in theranostics: how do we apply HDL's biology for precision medicine in atherosclerosis management?

B Uribe, Kepa / Benito-Vicente, Asier / Martin, Cesar / Blanco-Vaca, Francisco / Rotllan, Noemi

Biomaterials science

2021 Volume 9, Issue 9, Page(s) 3185–3208

Abstract: High-density lipoproteins (HDL) are key players in cholesterol metabolism homeostasis since they are responsible for transporting excess cholesterol from peripheral tissues to the liver. Imbalance in this process, due to either excessive accumulation or ... ...

Abstract	High-density lipoproteins (HDL) are key players in cholesterol metabolism homeostasis since they are responsible for transporting excess cholesterol from peripheral tissues to the liver. Imbalance in this process, due to either excessive accumulation or impaired clearance, results in net cholesterol accumulation and increases the risk of cardiovascular disease (CVD). Therefore, significant effort has been focused on the development of therapeutic tools capable of either directly or indirectly enhancing HDL-guided reverse cholesterol transport (RCT). More recently, in light of the emergence of precision nanomedicine, there has been renewed research interest in attempting to take advantage of the development of advanced recombinant HDL (rHDL) for both therapeutic and diagnostic purposes. In this review, we provide an update on the different approaches that have been developed using rHDL, focusing on the rHDL production methodology and rHDL applications in theranostics. We also compile a series of examples highlighting potential future perspectives in the field.
MeSH term(s)	Atherosclerosis/diagnosis ; Atherosclerosis/drug therapy ; Biology ; Cholesterol ; Humans ; Lipoproteins, HDL ; Precision Medicine
Chemical Substances	Lipoproteins, HDL ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2021-05-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d0bm01838d
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Article ; Online: Reverse Cholesterol Transport Dysfunction Is a Feature of Familial Hypercholesterolemia.

Escolà-Gil, Joan Carles / Rotllan, Noemí / Julve, Josep / Blanco-Vaca, Francisco

Current atherosclerosis reports

2021 Volume 23, Issue 6, Page(s) 29

Abstract: Purpose of review: We seek to establish whether high-density lipoprotein HDL metabolism and reverse cholesterol transport (RCT) impairment is an intrinsic feature of familial hypercholesterolemia (FH).: Recent findings: RCT from macrophages (m-RCT), ... ...

Abstract	Purpose of review: We seek to establish whether high-density lipoprotein HDL metabolism and reverse cholesterol transport (RCT) impairment is an intrinsic feature of familial hypercholesterolemia (FH). Recent findings: RCT from macrophages (m-RCT), a vascular cell type of major influence on atherosclerosis, is impaired in FH due to defective low-density lipoprotein receptor (LDLR) function via both the HDL- and LDL-mediated pathways. Potential mechanisms include impaired HDL metabolism, which is linked to increased LDL levels, as well as the increased transport of cellular unesterified cholesterol to LDL, which presents a defective catabolism. RCT dysfunction is consistently associated with mutation-positive FH linked to decreased HDL levels as well as impaired HDL remodeling and LDLR function. It remains to be explored whether these alterations are also present in less well-characterized forms of FH, such as cases with no identified mutations, and whether they are fully corrected by current standard treatments.
MeSH term(s)	Biological Transport ; Cholesterol ; Cholesterol, HDL/metabolism ; Humans ; Hyperlipoproteinemia Type II/genetics ; Lipoproteins, HDL ; Mutation ; Receptors, LDL/genetics ; Receptors, LDL/metabolism
Chemical Substances	Cholesterol, HDL ; Lipoproteins, HDL ; Receptors, LDL ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2021-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2057369-8
ISSN	1534-6242 ; 1523-3804
ISSN (online)	1534-6242
ISSN	1523-3804
DOI	10.1007/s11883-021-00928-1
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Zs.A 5534: Show issues

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Article ; Online: Phytosterols in Cancer: From Molecular Mechanisms to Preventive and Therapeutic Potentials.

Blanco-Vaca, Francisco / Cedó, Lídia / Julve, Josep

Current medicinal chemistry

2018 Volume 26, Issue 37, Page(s) 6735–6749

Abstract: Cancer is the second leading cause of death worldwide. Compelling evidence supports the hypothesis that the manipulation of dietary components, including plant compounds termed as phytochemicals, demonstrates certain important health benefits in humans, ... ...

Abstract	Cancer is the second leading cause of death worldwide. Compelling evidence supports the hypothesis that the manipulation of dietary components, including plant compounds termed as phytochemicals, demonstrates certain important health benefits in humans, including those in cancer. In fact, beyond their well-known cardiovascular applications, phytosterols may also possess anticancer properties, as has been demonstrated by several studies. Although the mechanism of action by which phytosterols (and derivatives) may prevent cancer development is still under investigation, data from multiple experimental studies support the hypothesis that they may modulate proliferation and apoptosis of tumor cells. Phytosterols are generally considered safe for human consumption and may also be added to a broad spectrum of food matrices; further, they could be used in primary and secondary prevention. However, few interventional studies have evaluated the relationship between the efficacy of different types and forms of phytosterols in cancer prevention. In this context, the purpose of this review was to revisit and update the current knowledge on the molecular mechanisms involved in the anticancer action of phytosterols and their potential in cancer prevention or treatment.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Humans ; Neoplasms/drug therapy ; Neoplasms/pathology ; Phytosterols/pharmacology
Chemical Substances	Phytosterols
Language	English
Publishing date	2018-04-20
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	1319315-6
ISSN	1875-533X ; 0929-8673
ISSN (online)	1875-533X
ISSN	0929-8673
DOI	10.2174/0929867325666180607093111
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Zs.A 4432: Show issues

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Article: NAD+-Increasing Strategies to Improve Cardiometabolic Health?

Blanco-Vaca, Francisco / Rotllan, Noemi / Canyelles, Marina / Mauricio, Didac / Escolà-Gil, Joan Carles / Julve, Josep

Frontiers in endocrinology

2022 Volume 12, Page(s) 815565

Abstract: Depleted nicotinamide adenine dinucleotide (NAD+) is a common hallmark of metabolic disorders. Therefore, NAD+-increasing strategies have evolved as a potential therapeutic venue to combat cardiometabolic diseases. Several forms of vitamin B3, i.e., ... ...

Abstract	Depleted nicotinamide adenine dinucleotide (NAD+) is a common hallmark of metabolic disorders. Therefore, NAD+-increasing strategies have evolved as a potential therapeutic venue to combat cardiometabolic diseases. Several forms of vitamin B3, i.e., nicotinamide and nicotinamide mononucleotide, and especially nicotinamide riboside, have attracted most interest as potentially safe and efficacious candidates for NAD+ restoration. Herein, we dissected the characteristics of the latest clinical trials testing the therapeutic potential of different vitamin B3 molecules to improve cardiometabolic health, with a special focus on randomized, placebo-controlled clinical trials performed in the context of obesity or other pathologies, mainly linked to cardiovascular system and skeletal muscle functionality. The favorable outcomes
MeSH term(s)	Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/prevention & control ; Humans ; Muscle, Skeletal/metabolism ; NAD/metabolism ; NAD/therapeutic use ; Obesity/metabolism
Chemical Substances	NAD (0U46U6E8UK)
Language	English
Publishing date	2022-01-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.815565
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Article ; Online: HDL-like-Mediated Cell Cholesterol Trafficking in the Central Nervous System and Alzheimer's Disease Pathogenesis.

Borràs, Carla / Mercer, Aina / Sirisi, Sònia / Alcolea, Daniel / Escolà-Gil, Joan Carles / Blanco-Vaca, Francisco / Tondo, Mireia

International journal of molecular sciences

2022 Volume 23, Issue 16

Abstract: The main aim of this work is to review the mechanisms via which high-density lipoprotein (HDL)-mediated cholesterol trafficking through the central nervous system (CNS) occurs in the context of Alzheimer's disease (AD). Alzheimer's disease is ... ...

Abstract	The main aim of this work is to review the mechanisms via which high-density lipoprotein (HDL)-mediated cholesterol trafficking through the central nervous system (CNS) occurs in the context of Alzheimer's disease (AD). Alzheimer's disease is characterized by the accumulation of extracellular amyloid beta (Aβ) and abnormally hyperphosphorylated intracellular tau filaments in neurons. Cholesterol metabolism has been extensively implicated in the pathogenesis of AD through biological, epidemiological, and genetic studies, with the
MeSH term(s)	Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Apolipoproteins E/metabolism ; Brain/metabolism ; Cholesterol/metabolism ; Cholesterol, HDL/metabolism ; Humans
Chemical Substances	Amyloid beta-Peptides ; Apolipoproteins E ; Cholesterol, HDL ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2022-08-19
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/ijms23169356
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Article ; Online: Consensus on lipoprotein(a) of the Spanish Society of Arteriosclerosis. Literature review and recommendations for clinical practice.

Delgado-Lista, Javier / Mostaza, Jose M / Arrobas-Velilla, Teresa / Blanco-Vaca, Francisco / Masana, Luis / Pedro-Botet, Juan / Perez-Martinez, Pablo / Civeira, Fernando / Cuende-Melero, Jose I / Gomez-Barrado, Jose J / Lahoz, Carlos / Pintó, Xavier / Suarez-Tembra, Manuel / Lopez-Miranda, Jose / Guijarro, Carlos

Clinica e investigacion en arteriosclerosis : publicacion oficial de la Sociedad Espanola de Arteriosclerosis

2024

Abstract: The irruption of lipoprotein(a) (Lp(a)) in the study of cardiovascular risk factors is perhaps, together with the discovery and use of proprotein convertase subtilisin/kexin type 9 (iPCSK9) inhibitor drugs, the greatest novelty in the field for decades. ... ...

Title translation	Consenso sobre lipoproteína (a) de la Sociedad Española de Arteriosclerosis. Revisión bibliográfica y recomendaciones para la práctica clínica.
Abstract	The irruption of lipoprotein(a) (Lp(a)) in the study of cardiovascular risk factors is perhaps, together with the discovery and use of proprotein convertase subtilisin/kexin type 9 (iPCSK9) inhibitor drugs, the greatest novelty in the field for decades. Lp(a) concentration (especially very high levels) has an undeniable association with certain cardiovascular complications, such as atherosclerotic vascular disease (AVD) and aortic stenosis. However, there are several current limitations to both establishing epidemiological associations and specific pharmacological treatment. Firstly, the measurement of Lp(a) is highly dependent on the test used, mainly because of the characteristics of the molecule. Secondly, Lp(a) concentration is more than 80% genetically determined, so that, unlike other cardiovascular risk factors, it cannot be regulated by lifestyle changes. Finally, although there are many promising clinical trials with specific drugs to reduce Lp(a), currently only iPCSK9 (limited for use because of its cost) significantly reduces Lp(a). However, and in line with other scientific societies, the SEA considers that, with the aim of increasing knowledge about the contribution of Lp(a) to cardiovascular risk, it is relevant to produce a document containing the current status of the subject, recommendations for the control of global cardiovascular risk in people with elevated Lp(a) and recommendations on the therapeutic approach to patients with elevated Lp(a).
Language	Spanish
Publishing date	2024-04-09
Publishing country	Spain
Document type	Practice Guideline
ISSN	1578-1879
ISSN (online)	1578-1879
DOI	10.1016/j.arteri.2024.03.002
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