Ana Paula Dantas

• PhD
• Researcher at Consorci Institut D'Investigacions Biomediques August Pi I Sunyer

Fibrillin 1 gene (Fbn1) mutations cause Marfan syndrome (MFS), triggering life-threatening aortic complications and multi-organ effects. MFS is increasingly linked to neurovascular complications, amplified by aortic surgery risks. However, the impact of MFS on the brain remains unclear, including the roles of sex, aging, and their contribution to c...

This comprehensive review aims to provide a thorough overview of the vital role that extracellular vesicles (EVs) play in endothelial dysfunction, particularly emphasizing how physiological factors—such as sex and aging—along with significant cardiovascular risk factors, influence this process. The review covers studies ranging from the first descr...

Background: Cardiovascular disease (CVD) remains the most common cause of mortality in chronic kidney disease (CKD) patients. Several studies suggest that the Mediterranean diet reduces the risk of CVD due to its influence on endothelial function, inflammation, lipid profile, and blood pressure. Integrating metabolomic and proteomic analyses of CKD...

Background Out-of-Hospital Cardiac Arrest (OHCA) supposes a main cause of disability and mortality worldwide. Between patients suffering OHCA, only a 10-20% can be successfully resuscitated and, between them, a 50% suffers of neurological sequelae. Mechanisms underlying brain damage seems to be strongly related with neuroinflammation, mediated by c...

Marfan syndrome (MFS), resulting from mutations in the fibrillin 1 gene (Fbn1), not only causes life-threatening aortic complications but also affects multiple organ systems. We aimed to investigate potential brain abnormalities and their contribution to worsened cerebral ischemic injury in a representative MFS mouse model. We assessed brain gene e...

Introduction: Surviving a myocardial infarction (MI) can have long-term consequences. Since damaged heart tissue and altered blood flow in chronic MI activates a myriad of both reparative and detrimental processes, understanding their associated mechanisms may impact outcomes and prevent heart failure. Extracellular vesicles (EVs) have great therag...

Background: In an acute myocardial infarction (AMI), dysfunctional endothelium releases thrombosis mediators, including von Willebrand Factor (vWF) and cellular microparticles. Metalloprotease-vWF-cleaving ADAMTS13 deficiency directs VWF-mediated thrombosis. While AMI often affects older individuals (<55 y/o), its rate is increasing among young pat...

Background: Out-of-Hospital Cardiac Arrest (OHCA) supposes a main cause of disability and mortality worldwide. Between OHCA patients, only a 10–20% can be successfully resuscitated and, between them, a 50% suffers neurological sequelae. Mechanisms underlying brain damage seems to be strongly related with neuroinflammation, mediated by classical (PC...

Despite the extensive clinical and scientific advances in prevention, diagnostics and treatment, cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality worldwide for people aged 65 and over. Of all ageing‐related diseases, CVD are responsible for almost one‐third of deaths in the elderly, being above all cancers combined....

Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models o...

Introduction: Endothelial Colony Forming Cells (ECFCs) present a dysfunctional and senescent phenotype in ischemic heart disease. However, the effect of myocardial infarction (MI), independently of common cardiovascular comorbidities (CCVC), on ECFCs functionality has not been evaluated up to date. Hypothesis: MI induces dysfunction of ECFCs with i...

Introducción y objetivos: Las células progenitoras endoteliales (ECFC) presentan disfunción después del infarto de miocardio (IM). Aunque se conoce que la disfunción endotelial es subyacente al IM, inducida por las comorbilidades cardiovasculares (CMCV), no hay estudios hasta la fecha que determinen cuál es el efecto del IM per se en la función de...

After myocardial infarction (MI), angiogenesis in the ischemic myocardium is essential for an optimal reparative process to limit the development of ventricular dysfunction. Cell-derived extracellular vehicles (EVs) are emerging as the next-generation strategy in tissue engineering. In this study, we aimed to determine the role of EVs derived from...

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Saludo Carlos III (ISCIII)-FEDER PI19/00264 Ministerio de Universidades - FPU19/04925 Background Inflammation and hypoxia are key players in the pathophysiology of Out-of-Hospital Cardiac Arrest (OHCA), and may be directly...

Introduction: The lower rates of cardiovascular disease in Southern Europe could be partially explained by the low prevalence of lipid-rich atheroma plaques. Consumption of certain foods affects the progression and severity of atherosclerosis. We investigated whether the isocaloric inclusion of walnuts within an atherogenic diet prevents phenotype...

Alpha-adrenergic receptors are crucial regulators of vascular hemodynamics and essential pharmacological targets for cardiovascular diseases. With aging, there is an increase in sympathetic activation, which could contribute to the progression of aging-associated cardiovascular dysfunction, including stroke. Nevertheless, there is little informatio...

Atherosclerosis is responsible for 20% of ischemic strokes, and severe carotid stenosis is associated with a higher incidence of first-ever and recurrent strokes. The release of pro-inflammatory mediators into the blood in severe atherosclerosis may aggravate endothelial dysfunction after stroke contributing to impair disease outcomes. We hypothesi...

Introduction: Early revascularization of infarcted zone is crucial to improve patient′s outcomes. Despite their primary actions, major lipid-lowering drugs may also reduce cardiovascular events by pleiotropic mechanisms. Hypothesis: Conventional (statin) and novel lipid-lowering therapies [(PSCK9-inhibitor (PCSK9i) and eicosatetraenoic acid (EPA)]...

Introduction: Right ventricular (RV) failure is the strongest determinant of survival in chronic pulmonary hypertension (PH), but its pathophysiological mechanisms remain unclear. Hypothesis: In addition to RV pressure overload, compounds liberated from the pulmonary vascular damage (identifiable by omics) may exert a detrimental effect on RV funct...

Aims Inhibitors of SGLT2 (SGLT2i) have shown a positive impact in patients with chronic heart failure and reduced ejection fraction (HFrEF). Nonetheless, the direct effects of SGLT2i on cardiac cells and how their association with main drugs used for HFrEF affect the behaviour and signalling pathways of myocardial fibroblasts are still unknown. We...

Moderate exercise has well-founded benefits in cardiovascular health. However, increasing, yet controversial, evidence suggests that extremely trained athletes may not be protected from cardiovascular events as much as moderately trained individuals. In our rodent model, intensive but not moderate training promoted aorta and carotid stiffening and...

MicroRNAs (miRNA) are major regulators of intercellular communication and key players in the pathophysiology of cardiovascular disease. This study aimed to determine the miRNA fingerprint in a cohort of 53 patients with acute myocardial infarction (AMI) with non-ST-segment elevation (NSTEMI) relative to miRNA expression in healthy controls (n = 51)...

Funding Acknowledgements Type of funding sources: None. Background Recovered out-of-hospital cardiac arrest (OHCA) is associated with high morbidity and mortality. Having prognostic tools within the first hours of admission to hospital is critical. The pH is a widespread arterial blood gas marker, but the influence of its respiratory/metabolic com...

Introduction: Preeclampsia is a multi-system disorder unique to pregnancy responsible for a great part of maternal and perinatal morbidity and mortality. The precise pathogenesis of this complex disorder is still unrevealed. Methods: We examined the pathophysiological pathways involved in early-onset preeclampsia, a specific subgroup representing i...

Endothelial cell dysfunction is the principal cause of several cardiovascular diseases that are increasing in prevalence, healthcare costs, and mortality. Developing a standardized, representative in vitro model of endothelial cell dysfunction is fundamental to a greater understanding of the pathophysiology, and to aiding the development of novel p...

Growing evidence indicates that perivascular tissue is critical to modulate vessel function. We hypothesized that the arachnoid membrane surrounding middle cerebral artery (MCA) regulates its function via sphingosine-1-phosphate (S1P)-induced vasoconstriction. The MCA from 3- to 9-month-old male and female wild-type (Oncine France 1 and C57BL/6) mi...

The exact mechanisms leading to myocardial injury in the coronavirus disease 2019 (COVID-19) are still unknown. In this retrospective observational study, we include all consecutive COVID-19 patients admitted to our center. They were divided into two groups according to the presence of myocardial injury. Clinical variables, Charlson Comorbidity Ind...

Preeclampsia is a pregnancy-specific multisystem disorder and a leading cause of maternal and perinatal morbidity and mortality. The exact pathogenesis of this multifactorial disease remains poorly defined. We applied proteomics analysis on maternal blood samples collected from 14 singleton pregnancies with early-onset severe preeclampsia and 6 unc...

Hypertension is the most important modifiable risk factor for stroke and is associated with poorer post-stroke outcomes. The antioxidant uric acid is protective in experimental normotensive ischaemic stroke. However, it is unknown whether this treatment exerts long-term protection in hypertension. We aimed to evaluate the impact of transient intral...

Reactive oxygen and nitrogen species are produced in a wide range of physiological reactions that, at low concentrations, play essential roles in living organisms. There is a delicate equilibrium between formation and degradation of these mediators in a healthy vascular system, which contributes to maintaining these species under non-pathological l...

Right ventricle (RV) dysfunction is a main determinant of morbidity and mortality in postcapillary pulmonary hypertension (PH). However, currently there are not available therapies. Since reduced nitric oxide (NO) availability and cyclic guanylate monophosphate (cGMP) levels are central in this disease, therapies targeting the NO pathway might have...

Objectives The presence of lipid-rich, unstable atheroma plaques in the vascular tree is the harbinger of cardiovascular events. There is a low prevalence of unstable atheroma plaques in Mediterranean countries. This might explain in part the lower rates of cardiovascular disease in Southern Europe compared to Northern Europe and US. Consumption of...

Despite the promising value of miRNAs in the diagnostic and prognostic of cardiovascular disease (CVD), recent meta-analyses did not support their potential. Methodological variances in studies may interfere with miRNA profile and affect their results. This study determines if the blood starting material is a source of variance in miRNA profile by...

Background Hypothermia has been associated with therapeutic benefits including reduced mortality and better neurologic outcomes in survivors of cardiac arrest. However, undesirable side effects have been reported in patients undergoing coronary interventions. Using a large animal model of temperature management, we aimed to describe how temperature...

Exosomes are key regulators of cell-to-cell communication, becoming valuable tool as disease biomarker and in the development of new therapeutic strategies. We aimed to determine the role of endothelial progenitor cell (EPC)-derived exosomes (EXO) in vascular remodelling induced by flow. C57BL/6 mice underwent chronic changes in flow by mesenteric...

Williams-Beuren syndrome (WBS) is a rare disorder caused by a heterozygous deletion of 26–28 contiguous genes that affects the brain and cardiovascular system. Here, we investigated whether WBS affects aortic structure and function in the complete deletion (CD) mouse model harbouring the most common deletion found in WBS patients. Thoracic aortas f...

Recent analysis of clinical trials on estrogen therapy proposes the existence of a therapeutic window of opportunity for the cardiovascular benefits of estrogens, which depend on women’s age and the onset of therapy initiation. In this study, we aimed to determine how vascular senescence and the onset of estrogen treatment influence the common caro...

Obstructive sleep apnea syndrome (OSA) promotes aortic dilatation, increased stiffness and accelerated atherosclerosis, but the mechanisms of vascular remodelling are not known. We aimed to assess vascular remodelling, its mechanisms, and the effect of mesenchymal stem cells (MSC) infusions in a clinically relevant rat model of chronic OSA involvin...

Exosomes are key regulators of cell-to-cell communication, becoming valuable tool as disease biomarker and in the development of new therapeutic strategies. We aimed to determine the role of endothelial progenitor cell (EPC)-derived exosomes (EXO) in vascular remodeling induced by flow. C57BL/6 mice underwent chronic changes in flow by mesenteric r...

Circulating exosomes have a great impact in human health as a biomarker or as messengers in intercellular signaling. In this study we aimed to determine how miRNA profile in circulating exosomes interfere with angiogenic phenotype of endothelial cell (EC) during acute event of coronary syndrome. Exosomes were purified from serum of patients with no...

Uric acid (UA) is a promising protective treatment in ischaemic stroke, but the precise molecular targets underlying its in vivo beneficial actions remain unclear. High concentrations of UA inhibit angiogenesis of cultured endothelial cells via Krüppel-like factor 2 (KLF)-induced downregulation of vascular endothelial growth factor (VEGF), a pro-an...

There is scarce evidence for pulmonary artery denervation (PADN) as a potential treatment for chronic postcapillary pulmonary hypertension (PH). We aimed to perform a proof-of-concept of PADN in a translational model of chronic PH. Nineteen pigs with chronic postcapillary PH (secondary to pulmonary vein banding) were randomized to surgical-PADN (us...

Conjugated equine estrogens (CEE) have been widely used by women who seek to relieve symptoms of menopause. Despite evidence describing protective effects against risk factors for cardiovascular diseases by naturally occurring estrogens, little is known about the vascular effects of equilin, one of the main components of CEE and not physiologically...

Objective: The aim of this study was to perform a comprehensive assessment of the placental aging process through senescence and apoptotic markers in late-onset small fetuses classified as SGA or FGR. Study design: A prospective nested case-control study in singleton pregnancies delivering at term including 21 normally grown fetuses and 36 small...

Resumen Introducción y objetivos En el infarto agudo de miocardio con elevación del segmento ST, el ADN libre circulante podría originarse de los leucocitos activados en la lesión coronaria. El objetivo fue investigar la relación entre el ADN libre y la reperfusión coronaria. Métodos Se incluyó a 116 pacientes, tratados con angioplastia primaria...

Postmenopausal period has been associated to different symptoms such as hot flashes, vulvovaginal atrophy, hypoactive sexual desire disorder (HSDD) and others. Clinical studies have described postmenopausal women presenting HSDD can benefit from the association of testosterone to conventional hormonal therapy. Testosterone has been linked to develo...

Introduction and objectives: Cell-free DNA (cfDNA) in ST-segment elevation myocardial infarction might originate from hyperactivated leukocytes at the coronary lesion. Our aim was to investigate the relationship between cfDNA and coronary reperfusion. Methods: We studied 116 patients treated with primary angioplasty using thrombus aspiration. Coro...

Background/aims: Estrogen signalling plays an important role in vascular biology as it modulates vasoactive and metabolic pathways in endothelial cells. Growing evidence has also established microRNA (miRNA) as key regulators of endothelial function. Nonetheless, the role of estrogen regulation on miRNA profile in endothelial cells is poorly under...

Endothelium and Cardiovascular Diseases: Vascular Biology and Clinical Syndromes provides an in-depth examination of the role of endothelium and endothelial dysfunction in normal vascular function, and in a broad spectrum of clinical syndromes, from atherosclerosis, to cognitive disturbances and eclampsia. The endothelium is a major participant in...

Marfan syndrome (MFS) is a hereditary disorder of the connective tissue that causes life-threatening aortic aneurysm, which initiates at the aortic root and can progress into the ascending portion. However, analysis of ascending aorta reactivity in animal models of MFS has remained elusive. Epidemiologic evidence suggests that although MFS is equal...

Peroxynitrite (ONOO-) is crucially involved in the initiation and progression of human cardiovascular disease. Selenium is an essential micronutrient that plays a key role in redox regulation and antioxidant defence. Synthetic organoselenium compounds such as ebselen can mimic the function of endogenous antioxidant selenoenzymes, but ebselen can be...

Standard hormone therapy for menopausal women [conjugated equine estrogen (CEE) 0.625 mg] has been associated with increased risk of venous thrombosis. Regimens containing lower CEE dose (0.30 mg) have been clinically used to decrease side effects of supra-physiological doses of estrogen. In this study, we determined the effects of standard (SD) an...

Background Autologous adipose tissue–derived mesenchymal stem cells (ATMSCs) therapy is a promising strategy to improve post–myocardial infarction outcomes. In a porcine model of acute myocardial infarction, we studied the long‐term effects and the mechanisms involved in allogeneic ATMSCs administration on myocardial performance. Methods and Resul...

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Through specific base pairing with their targets messenger RNAs (mRNA), miRNA can modify cell phenotype and function. Several miRNAs are aberrantly expressed in diseased arteries and may influence different features of vascular remodeling,...

Background: Therapeutic hypothermia (HT) in out-of-hospital cardiac arrest STEMI patients aims to improve their neurological prognosis, but it has been associated with slow coronary flow and cardiac thrombotic events. We sought to serially assess endothelial function during the first 48h after admission in out-of-hospital cardiac arrest STEMI pati...

Este estudio sugiere que existe un footprint característico de micro-ARN en pacientes con IAMSEST en el momento del infarto con un patrón distinto respecto al paciente estable al año de seguimiento y respecto a los voluntarios sanos. Se desconoce el mecanismo fisiopatológico implicado entre el cambio en el patrón de micro-ARN y el IAM, siendo una h...

Aging is a cardiovascular risk factor partially related to activation of the Renin-Angiotensin System (RAS). RAS activation is also influenced by sex. In this regard, our study aims to determine whether sex-associated differences in RAS contribute to a differential regulation of vascular aging and associated dysfunction. Male and female outbreed CD...

Objective: In vascular smooth muscle the Rho signaling pathway is highly activated in a variety of vascular diseases. Our aim was to check the involvement of Rho kinase (ROCK) on the increased vascular contractions induced by ageing in female mouse aorta. Design and method: Female senescence-accelerated mice (SAMP8, n = 21) or the control, SAM-r...

Aim: Increased thromboxane A2 and peroxynitrite are hallmarks of cerebral ischemia/reperfusion (I/R). Stimulation of thromboxane/prostaglandin receptors (TP) attenuates endothelium-derived hyperpolarization (EDH). We investigated whether EDH-type middle cerebral artery (MCA) relaxations following TP stimulation are altered after I/R and the influe...

Marfan syndrome (MFS) is a connective tissue disorder that is often associated with fibrillin-1 (Fbn1) gene mutation and characterized by cardiovascular alterations, predominantly ascending aortic aneurysms. Although neurovascular complications are uncommon in MFS, the improvement in Marfan patients' life expectancy is revealing other secondary alt...

This study investigates the effects of aging and/or ovariectomy on vascular reactivity to thromboxane A2 (TXA2) receptor stimulation with U46619, and the modulation by nitric oxide (NO) and cyclooxygenase (COX) in aorta from female senescence-accelerated mice (SAMP8) and from senescence resistant mice (SAMR1). Five-month-old female SAMR1 and SAMP8...

Introduction: Moderate aerobic exercise reduces atherosclerotic burden. However, recent data show increased cardiovascular disease burden and mortality in the most trained individuals. Aim: To assess vascular remodeling after very high intensity training. Methods: Wistar rats underwent very high (INT, 60min 60cm/s, n=20) or moderate intensity (MOD,...

Age is the most important risk factor for cardiovascular diseases. A key requisite to develop new interventions for age-related conditions is the availability of preclinical murine models. We propose prone senescence-accelerated mice (SAMP8) to study vascular ageing in a convenient and standard time course. Our aim was to investigate the effects of...

Ischemia impairs blood supply to the brain and reperfusion is important to restore cerebral blood flow (CBF) and rescue neurons from cell death. However, reperfusion can induce CBF values exceeding the basal values prior to ischemia. This hyperemic effect has been associated with a worse ischemic brain damage, albeit the mechanisms that contribute...

Testosterone has been added to hormone replacement therapy to treat sexual dysfunction in postmenopausal women. Whereas estrogen has been associated with vascular protection, the vascular effects of testosterone are contradictory and the effects of its association with estrogen are largely unknown. In this study we determined the effects of testost...