Cardiovascular Disease States Research Articles

MicroRNA-181 in cardiovascular disease: Emerging biomarkers and therapeutic targets.

Cardiovascular disease (CVD) is the leading cause of death worldwide. MicroRNAs (MiRNAs) have attracted considerable attention for their roles in several cardiovascular disease states, including both the physiological and pathological processes. In this review, we will briefly describe microRNA-181 (miR-181) transcription and regulation and summarize recent findings on the roles of miR-181 family members as biomarkers or therapeutic targets in different cardiovascular-related conditions, including atherosclerosis, myocardial infarction, hypertension, and heart failure. Lessons learned from these studies may provide new theoretical foundations for CVD.

Cost-effectiveness study of FIB-4 followed by transient elastography screening strategy for advanced hepatic fibrosis in a NAFLD at-risk population.

The cost-effectiveness to screen hepatic fibrosis in at-risk population as recommended by several professional societies has been limited. This study aimed to investigate the cost-effectiveness of this screening strategy in the expanded at-risk population recently proposed by several societies. A combined model of the decision tree and Markov models was developed to compare expected costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) between screening and no screening groups. The model included liver disease-related health states and cardiovascular disease (CVD) states as a base-case analysis. Screening strategy consisted of fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE) and intensive lifestyle intervention (ILI) as a treatment for diagnosed patients. Cost-effectiveness analysis showed that screening the at-risk population entailed $298 incremental costs and an additional 0.0199 QALY per patient compared to no screening (ICER $14 949/QALY). Screening was cost-effective based on the implicit ICER threshold of $25 000/QALY in Korea. When the effects of ILI on CVD and extrahepatic malignancy were incorporated into the cost-effectiveness model, the ICER decreased by 0.85 times from the base-case analysis (ICER $12 749/QALY). In contrast, when only the effects of liver disease were considered in the model, excluding cardiovascular disease effects, ICER increased from the baseline case analysis to $16 305. Even when replacing with medical costs in Japan and U.S., it remained cost-effective with the estimate below the countries' ICER threshold. Our study provides compelling evidence supporting the cost-effectiveness of FIB-4-based screening the at-risk population for advanced hepatic fibrosis.

Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review.

Blood metabolomics profiling using mass spectrometry has emerged as a powerful approach for investigating non-cancer diseases and understanding their underlying metabolic alterations. Blood, as a readily accessible physiological fluid, contains a diverse repertoire of metabolites derived from various physiological systems. Mass spectrometry offers a universal and precise analytical platform for the comprehensive analysis of blood metabolites, encompassing proteins, lipids, peptides, glycans, and immunoglobulins. In this comprehensive review, we present an overview of the research landscape in mass spectrometry-based blood metabolomics profiling. While the field of metabolomics research is primarily focused on cancer, this review specifically highlights studies related to non-cancer diseases, aiming to bring attention to valuable research that often remains overshadowed. Employing natural language processing methods, we processed 507 articles to provide insights into the application of metabolomic studies for specific diseases and physiological systems. The review encompasses a wide range of non-cancer diseases, with emphasis on cardiovascular disease, reproductive disease, diabetes, inflammation, and immunodeficiency states. By analyzing blood samples, researchers gain valuable insights into the metabolic perturbations associated with these diseases, potentially leading to the identification of novel biomarkers and the development of personalized therapeutic approaches. Furthermore, we provide a comprehensive overview of various mass spectrometry approaches utilized in blood metabolomics research, including GC-MS, LC-MS, and others discussing their advantages and limitations. To enhance the scope, we propose including recent review articles supporting the applicability of GC×GC-MS for metabolomics-based studies. This addition will contribute to a more exhaustive understanding of the available analytical techniques. The Integration of mass spectrometry-based blood profiling into clinical practice holds promise for improving disease diagnosis, treatment monitoring, and patient outcomes. By unraveling the complex metabolic alterations associated with non-cancer diseases, researchers and healthcare professionals can pave the way for precision medicine and personalized therapeutic interventions. Continuous advancements in mass spectrometry technology and data analysis methods will further enhance the potential of blood metabolomics profiling in non-cancer diseases, facilitating its translation from the laboratory to routine clinical application.

Abdominal Aortic Aneurysm Response to Interleukin-10 Hydrogel-Based “Bio-Ink” Therapy in Rodent Models

Abdominal Aortic Aneurysms (AAA) are the pathological expansion of the aorta, which can rupture and cause significant mortality. Approximately 200,000 AAA cases occur annually in the US, with more than 15,000 cases resulting in death. Risk factors for AAA are similar to those of cardiovascular disease states, particularly cigarette smoking, and AAA patients are generally elderly, Caucasian males. Currently, no medical therapy exists for AAA outside of surgical intervention. We previously hypothesized that the early initiation and propagation of stages in AAA development are inflammatory driven. This process results in a weaker aortic wall, whichwe have evidenced through increased elastin breakdown products and inflammatory markers in AAA patients in comparison to matched controls. This project investigated the use of a novel anti-inflammatory hydrogel to ameliorate AAA progression.
 Our study uses a gelatin-based biodegradable bio-ink containing the anti-inflammatory cytokine interleukin-10 (IL-10), which was applied to the aorta with a novel hydrogel extruding “BIOPENCIL” device. We used a previously described rodent model consisting of intra-luminal injection of elastase in the infrarenal aorta combined with topical application of calcium chloride; alternatively, topical calcium chloride was used alone for AAA development. The BIOPENCIL was used to deliver the hydrogel containing IL-10 or control at the time of AAA creation. The animals were euthanized 14 or 21 days post-procedure and evaluated for AAA volume, surface area, and diameter alongside molecular analyses to evaluate for immunological changes between control and treatment groups. We predict that the rodent groups treated with IL-10 will not have AAA expansion, while the control group will see AAA expansion. This is based onlongitudinal data from weekly ultrasounds and will be confirmed with microCT.

Walking pace and the time between the onset of noncommunicable diseases and mortality: a UK Biobank prospective cohort study

To estimate time spent in various cardiovascular disease (CVD) and cancer states, according to self-reported walking pace. In total, 391,744 UK Biobank participants were included (median age=57 years; 54.7% women). Data were collected 2006-2010, with follow-up collected in 2021. Usual walking pace was self-defined as slow, steady, average, or brisk. Multistate modeling determined the transition rate and mean sojourn time in and across three different states (healthy, CVD or cancer, and death) upon a time horizon of 10 years. The mean sojourn time in the healthy state was longer, while that in the CVD orcancer state was shorter in individuals reporting an average or brisk walking pace (vs. slow). A 75-year-old woman reporting a brisk walking pace spent, on average, 8.4 years of the next 10 years in a healthy state; an additional 8.0 (95% CI: 7.3, 8.7) months longer than a 75-year-old woman reporting a slow walking pace. This corresponded to 4.3 (3.7, 4.9) fewer months living with CVDorcancer. Similar results were seen in men. Adults reporting an average or brisk walking pace at baseline displayed a lower transition to disease development and a greater proportion of life lived without CVDorcancer. Research was conducted using the UK Biobank resource under Application #33266. The UK Biobank resource can be accessed by researchers on application. Variables derived for this study have been returned to the UK Biobank for future applicants to request. No additional data are available.

The Therapeutic Potential of Targeting Ferroptosis in the Treatment of Mitochondrial Cardiomyopathies and Heart Failure.

Ferroptosis is a form of iron-regulated cell death implicated in a wide array of diseases, including heart failure, hypertension, and numerous cardiomyopathies. In addition, mitochondrial dysfunction has been associated with several of these same disease states. However, the role of the mitochondrion in ferroptotic cell death remains debated. As a major regulator of cellular iron levels, the mitochondria may very well play a crucial role in the mechanisms behind ferroptosis, but at this point, this has not been adequately defined. Emerging evidence from our laboratory and others indicates a critical role of mitochondrial Sirtuin 3, a deacetylase linked with longevity and protection against numerous conditions, in the prevention of cardiovascular diseases. Here, we provide a brief overview of the potential roles of Sirtuin 3 in mitochondrial iron homeostasis and its contribution to the mitochondrial cardiomyopathy of Friedreich's ataxia and diabetic cardiomyopathy. We also discuss the current knowledge of the involvement of ferroptosis and the mitochondria in these and other cardiovascular disease states, including doxorubicin-induced cardiomyopathy, and provide insight into areas requiring further investigation.

Highlighting Fibroblasts Activation in Fibrosis: The State-of-The-Art Fibroblast Activation Protein Inhibitor PET Imaging in Cardiovascular Diseases.

Fibrosis is a common healing process that occurs during stress and injury in cardiovascular diseases. The evolution of fibrosis is associated with cardiovascular disease states and causes adverse effects. Fibroblast activation is responsible for the formation and progression of fibrosis. The incipient detection of activated fibroblasts is important for patient management and prognosis. Fibroblast activation protein (FAP), a membrane-bound serine protease, is almost specifically expressed in activated fibroblasts. The development of targeted FAP-inhibitor (FAPI) positron emission tomography (PET) imaging enabled the visualisation of FAP, that is, incipient fibrosis. Recently, research on FAPI PET imaging in cardiovascular diseases increased and is highly sought. Hence, we comprehensively reviewed the application of FAPI PET imaging in cardiovascular diseases based on the state-of-the-art published research. These studies provided some insights into the value of FAPI PET imaging in the early detection of cardiovascular fibrosis, risk stratification, response evaluation, and prediction of the evolution of left ventricular function. Future studies should be conducted with larger populations and multicentre patterns, especially for response evaluation and outcome prediction.

Metformin and SGLT2i as First-line Combination Therapy in Type 2 Diabetes: A Real-world Study With a Focus on Ethnicity

Suboptimal glucose control early in the diagnosis of type 2 diabetes (T2D) is strongly associated with subsequent morbidity and mortality, termed the 'glycaemic legacy'. Additionally, it is known that Asian and Black individuals are at increased risk of T2D, and its associated complications compared to their White counterparts. However, ethnicity does not currently feature in the treatment algorithm of T2D, unlike in other cardiovascular disease states such as hypertension. We therefore sought to evaluate the real-world impact of early intensive treatment with combination therapy on cardiorenal outcomes compared to standard treatment in T2D, with a focus on ethnicity. We performed a retrospective cohort study of all patients aged 18 or over with T2D using the TriNetX platform. TriNetX is a global collaborative network providing access to real time, anonymised medical records. We included patients who were initiated with Metformin and an SGLT2i within one month of diagnosis of T2D and compared this cohort with individuals who received Metformin only for a period of at least 1 year. We evaluated cardiovascular and renal outcomes at three years and stratified by ethnicity. We excluded individuals with a personal history of an outcome of interest. We identified 49,651 individuals with T2D who were treated with Metformin and an SGLT2i and 1,028,806 patients with T2D who were treated with Metformin alone. A total of 98,094 individuals were included in the core analysis. The Metformin only group had a greater risk of mortality (RR 1.44, [95% CI 1.34-1.55], P<0.0001), CKD (RR 1.10, [95% CI 1.04-1.16], P = 0.0004), diabetic nephropathy (RR 1.06, [95% CI 1.01-1.12], P = 0.0239), heart failure (RR 1.13, [95% CI 1.07-1.21], P < 0.0001) and hospitalisation (RR 1.24, [95% CI 1.21-1.27], P < 0.0001) compared to individuals treated with Metformin and SGLT2i. Black individuals had a reduced risk of mortality (RR 0.71, [95% CI 0.55-0.92], P = 0.0099) and IHD (RR 0.73, [95% CI 0.64-0.84], P < 0.0001) compared to White individuals. Asian individuals had a reduced risk of heart failure (RR 0.61, [95% CI 0.41-0.91], P = 0.0134) and hospitalisation (RR 0.76, [95% CI 0.66-0.87], P = 0.0001) compared to White individuals. Initial combination treatment within the first year of T2D diagnosis confers favourable cardio-metabolic outcomes when compared to standard therapy, even in patients without established cardiovascular disease. Black and Asian individuals in particular demonstrate a greater degree of benefit compared to White individuals. Further prospective studies with a focus on ethnicity are now required to validate these findings.

Abstract P2103: Cardiac Fibroblast-specific Role Of PTBP1 In Maintaining Heart Function

Cardiac fibroblasts (CFs) are the primary nonmyocyte in the heart that maintain cardiac homeostasis by regulating myocardial function and cardiac remodeling. CFs secrete an extracellular matrix to stabilize the myocardial wall while maintaining the heart’s mechanical integrity during development and pathogenesis. Developmental and pathogenic transitions are directed through CFs by transcriptional and post-transcriptional modifications, such as alternative splicing. Alternative splicing is a central element in post-transcriptional gene regulation and proteomic diversity. Impaired and aberrant splicing is known to cause developmental defects and drive cardiac pathogenesis. RNA binding proteins (RBPs), which function as alternative splicing factors, are upregulated in cardiovascular disease states. While nearly a third of all CF gene regulation changes during cardiac fibrosis are subject to transcriptional regulation via RBPs, the role of CF specific splicing RBPs in the adult heart and during cardiac fibrosis is unknown. Our group previously identified high expression of well-known RBP and splicing factor polypyrimidine tract-binding protein (PTBP1) in CFs when compared to cardiomyocytes in the adult heart. With single cell transcriptomics we found PTBP1 regulates CF identity and plasticity, suggesting an emergent role of PTBP1 within CF biology. We hypothesize PTBP1 is essential for maintaining cardiac fibroblast function in the adult heart. Preliminary in vitro data suggests partial Ptbp1 knockdown impacts mechanical function by decreasing overall CF migration. To further characterize PTBP1 in vivo , we have validated our novel mouse model to specifically delete PTBP1 from CFs in adult mice. Following PTBP1 deletion, we will utilize an established model of fibrosis by Angiotensin II osmotic minipumps to characterize the CF specific PTBP1 loss during fibrosis. We will evaluate CF biology with our in vitro and in vivo models to examine PTBP1’s physiological and mechanistic role in maintaining CF biology during cardiac homeostasis and cardiac fibrosis pathogenesis.

Expanded Use of Sodium Glucose Co-Transporter 2 Inhibitors: Evidence Beyond Heart Failure with Reduced Ejection Fraction.

Following the results observed in the DAPA-HF trial and subsequent FDA approval of dapagliflozin in patients living with heart failure with reduced ejection fraction (HFrEF), numerous trials quickly began to assess the effects of sodium glucose co-transporter 2 inhibitors (SGLT2i) in a wide range of CV (CV) conditions. Since publication of those findings, multiple SGLT2i have demonstrated benefit in patients regardless of left ventricular ejection fraction (LVEF) - allowing the drug class to establish itself within the first-line of guideline directed medication therapy. Although the full mechanistic properties of SGLT2i in heart failure (HF) has yet to be fully understand, benefits in other disease states have continued to emerge over the past decade. This review summarizes the findings of 14 clinical trials investigating the use of SGLT2i in various cardiovascular (CV) disease states, with a special focus on HF with preserved ejection fraction (HFpEF) and acute decompensated HF (ADHF). Additionally, studies assessing the CV-related mechanisms, cost-effectiveness, and exploratory effects of dual SGLT1/2 blockade are described. A review of select ongoing trials has also been incorporated to further characterize the research landscape with this medication class. The aim of this review is to serve as a comprehensive tool for healthcare providers to better understand how this class of diabetes medications established its place in the treatment of HF.

Evaluation of contemporary methods to determine vascular impedance.

The past decade has seen considerable growth in therapeutics and device technologies to treat patients with hypertension and other cardiovascular disease states. Uncoupling ventriculo-arterial interactions in these patients, however, is often complex and not adequately accounted for by arterial pressure or vascular resistance measurement alone. In reality, the global vascular load presented to the left ventricle (LV) includes both steady-state and pulsatile components. Whereas steady-state load is best represented by the vascular resistance, pulsatile load, which incorporates wave reflections and arterial stiffness, may oscillate during various phases of the cardiac cycle and is best determined by the vascular impedance (Z). In recent years, measurement of Z has become more readily accessible through an array of simultaneous applanation tonometry, echocardiography and cardiac magnetic resonance (CMR) techniques. In the following review, we evaluate existing and newer methods to assess Z so as to better understand the pulsatile characteristics of the human circulation in hypertension and other cardiovascular disease states.

Cardio-Thyrotoxicosis Syndrome: A Review of Thyrotoxic Cardiovascular Disease.

Thyrotoxicosis, an endocrine disorder characterized by elevated serum thyroid hormone levels of tri-iodothyronine (T3) and/or thyroxine (T4), can impact cardiovascular health in several ways. The cardiovascular system is often severely targeted by the thyrotoxic state, and the term "Cardio-thyrotoxic syndrome" has been proposed to encompass the various cardiovascular disease states resulting from thyrotoxicosis. In this review, we discuss various cardiovascular disorders resulting from the effects of thyrotoxicosis. It is important to keep a high index of suspicion for thyroid disorder in the setting of new atrial fibrillation, heart failure, and tachycardia-induced cardiomyopathy. Management of cardio-thyrotoxicosis involves control of heart rate and blood pressure and treatment of acute cardiovascular complications. Thyroid-specific therapy to achievea euthyroid state will not only improve but even potentially reverse cardiovascular abnormalities.

Novel Oxidative Stress Biomarkers with Risk Prognosis Values in Heart Failure.

Oxidative stress (OS) is mediated by reactive oxygen species (ROS), which in cardiovascular and other disease states, damage DNA, lipids, proteins, other cellular and extra-cellular components. OS is both initiated by, and triggers inflammation, cardiomyocyte apoptosis, matrix remodeling, myocardial fibrosis, and neurohumoral activation. These have been linked to the development of heart failure (HF). Circulating biomarkers generated by OS offer potential utility in patient management and therapeutic targeting. Novel OS-related biomarkers such as NADPH oxidases (sNox2-dp, Nrf2), advanced glycation end-products (AGE), and myeloperoxidase (MPO), are signaling molecules reflecting pathobiological changes in HF. This review aims to evaluate current OS-related biomarkers and their associations with clinical outcomes and to highlight those with greatest promise in diagnosis, risk stratification and therapeutic targeting in HF.

Endothelial cell-specific roles for tetrahydrobiopterin in myocardial function, cardiac hypertrophy, and response to myocardial ischemia-reperfusion injury.

The cofactor tetrahydrobiopterin (BH4) is a critical regulator of nitric oxide synthase (NOS) function and redox signaling, with reduced BH4 implicated in multiple cardiovascular disease states. In the myocardium, augmentation of BH4 levels can impact on cardiomyocyte function, preventing hypertrophy and heart failure. However, the specific role of endothelial cell BH4 biosynthesis in the coronary circulation and its role in cardiac function and the response to ischemia has yet to be elucidated. Endothelial cell-specific Gch1 knockout mice were generated by crossing Gch1fl/fl with Tie2cre mice, generating Gch1fl/flTie2cre mice and littermate controls. GTP cyclohydrolase protein and BH4 levels were reduced in heart tissues from Gch1fl/flTie2cre mice, localized to endothelial cells, with normal cardiomyocyte BH4. Deficiency in coronary endothelial cell BH4 led to NOS uncoupling, decreased NO bioactivity, and increased superoxide and hydrogen peroxide productions in the hearts of Gch1fl/flTie2cre mice. Under physiological conditions, loss of endothelial cell-specific BH4 led to mild cardiac hypertrophy in Gch1fl/flTie2cre hearts. Endothelial cell BH4 loss was also associated with increased neuronal NOS protein, loss of endothelial NOS protein, and increased phospholamban phosphorylation at serine-17 in cardiomyocytes. Loss of cardiac endothelial cell BH4 led to coronary vascular dysfunction, reduced functional recovery, and increased myocardial infarct size following ischemia-reperfusion injury. Taken together, these studies reveal a specific role for endothelial cell Gch1/BH4 biosynthesis in cardiac function and the response to cardiac ischemia-reperfusion injury. Targeting endothelial cell Gch1 and BH4 biosynthesis may provide a novel therapeutic target for the prevention and treatment of cardiac dysfunction and ischemia-reperfusion injury.NEW & NOTEWORTHY We demonstrate a critical role for endothelial cell Gch1/BH4 biosynthesis in coronary vascular function and cardiac function. Loss of cardiac endothelial cell BH4 leads to coronary vascular dysfunction, reduced functional recovery, and increased myocardial infarct size following ischemia/reperfusion injury. Targeting endothelial cell Gch1 and BH4 biosynthesis may provide a novel therapeutic target for the prevention and treatment of cardiac dysfunction, ischemia injury, and heart failure.

Non-invasive mapping of systemic neutrophil dynamics upon cardiovascular injury

Neutrophils play a complex role during onset of tissue injury and subsequent resolution and healing. To assess neutrophil dynamics upon cardiovascular injury, here we develop a non-invasive, background-free approach for specific mapping of neutrophil dynamics by whole-body magnetic resonance imaging using targeted multimodal fluorine-loaded nanotracers engineered with binding peptides specifically directed against murine or human neutrophils. Intravenous tracer application before injury allowed non-invasive three-dimensional visualization of neutrophils within their different hematopoietic niches over the entire body and subsequent monitoring of their egress into affected tissues. Stimulated murine and human neutrophils exhibited enhanced labeling due to upregulation of their target receptors, which could be exploited as an in vivo readout for their activation state in both sterile and nonsterile cardiovascular inflammation. This non-invasive approach will allow us to identify hidden origins of bacterial or sterile inflammation in patients and also to unravel cardiovascular disease states on the verge of severe aggravation due to enhanced neutrophil infiltration or activation.

Changes in circulating sirtuin 1 after bariatric surgery

Background and aimsObesity is associated with chronic inflammation and oxidative stress. Weight loss after bariatric surgery improves the inflammatory state and risk of cardiovascular disease. Improvement in metabolic dysfunction might be associated with changes in the activity of sirtuin 1 (SIRT1) and we aimed to investigate the effect of bariatric surgery on its circulating levels. Methods and resultsThis is a sub-study of a prospective cohort study, including 110 subjects with morbid obesity. The surgical procedure was either laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Blood was sampled at inclusion and six and 12 months after surgery. SIRT1 was measured in EDTA plasma with an enzyme-linked immunosorbent assay. The mean age in the population was 43 years, 80% were women and mean body mass index (BMI) was 38.8 kg/m2. RYGB and SG were performed in 89 and 21 subjects, respectively. SIRT1 concentration was significantly reduced from baseline to six and 12 months after surgery, with mean values (SD) 156.8 (82.6), 119.5 (65.6) and 94.9 (45.6) ng/mL, respectively, (p ≤ 0.002, all), accompanied by significant reductions in C-reactive protein (CRP), BMI and triglycerides from inclusion (p < 0.001, all). Type of surgery did not differently modify SIRT1 levels (p = 0.09). CRP and triglycerides were both positively predictive of SIRT1 levels (p ≤ 0.001, both). ConclusionSIRT1 concentration was significantly lower six and 12 months after bariatric surgery. CRP and triglycerides independently predicted SIRT1 levels, suggesting that reduction in SIRT1 levels might not intrinsically be related to weight reduction, but to improvement in metaflammation.

Branched-chain amino acids in cardiovascular disease.

Research conducted in the past 15 years has yielded crucial insights that are reshaping our understanding of the systems physiology of branched-chain amino acid (BCAA) metabolism and the molecular mechanisms underlying the close relationship between BCAA homeostasis and cardiovascular health. The rapidly evolving literature paints a complex picture, in which numerous tissue-specific and disease-specific modes of BCAA regulation initiate a diverse set of molecular mechanisms that connect changes in BCAA homeostasis to the pathogenesis of cardiovascular diseases, including myocardial infarction, ischaemia-reperfusion injury, atherosclerosis, hypertension and heart failure. In this Review, we outline the current understanding of the major factors regulating BCAA abundance and metabolic fate, highlight molecular mechanisms connecting impaired BCAA homeostasis to cardiovascular disease, discuss the epidemiological evidence connecting BCAAs with various cardiovascular disease states and identify current knowledge gaps requiring further investigation.

In patients with cardiovascular disease and heart failure dental state (tooth loss) may exacerbate inflammatory syndrome

Background and Aims: We hypothesized that dental state overall appreciated by simple counting of dental loss may have a role in cardiac failure pathogenesis by chronic inflammation generated by gum chronic infection (periodontosis, periodontitis).

HYPERTENSIVE PATIENTS WITH ANGINA AND NON-OBSTRUCTIVE CORONARY ARTERY DISEASE ARE CHARACTERIZED BY INCREASED SYMPATHETIC NERVOUS SYSTEM ACTIVATION

Objective: There are data supporting that sympathetic nervous system (SNS) is implicated in the regulation of endothelium function and vascular tone in different cardiovascular disease states. Patients with hypertension and angina frequently present non-obstructive coronary artery disease (CAD) in angiography. The aim of our study was to assess the level of SNS activation in hypertensive patients with angina and non-obstructive CAD, in hypertensives without angina and normotensive controls. Design and method: Our population consisted of 10 treated hypertensive patients with angina who had non-obstructive CAD in coronary angiography [7 females, mean age: 60.5 ± 9.6 years, office blood pressure (BP): 157/93 ± 13/11 mmHg], 16 treated hypertensive patients without angina (9 females, mean age: 59.5 ± 7.5 years, office BP:142/88 mmHg) and 11 normotensive individuals without angina (8 females, mean age: 51.8 ± 11 years, BP:125/87 mmHg). In all participants, muscle sympathetic nerve activity (MSNA) was assessed. Results: Hypertensives with angina and non-obstructive CAD (n = 10) compared to hypertensive patients without angina (n = 16) and normotensives without angina (n = 11) exhibited higher levels of MSNA (57.6 ± 6.1 vs 43 ± 8.4 vs 45 ± 9.5 bursts per minute, respectively; p &lt; 0.01 for all) and 24-h ambulatory BP (144/83 ± 20/14 vs 141/83 ± 7/10 vs to normotensives 125/81 ± 7/6 mmHg, respectively; p &lt; 0.001 for all). There were no differences in renal function between groups and no gender related effects on MSNA values (p = NS). Conclusions: Hypertensive patients with angina and non-obstructive CAD are characterized by higher SNS drive compared to hypertensives without angina and normotensive controls, as reflected by MSNA levels. These preliminary results indicate that therapies targeting SNS tone could be of potential clinical benefit in this high-risk hypertension phenotype.

Exposure of Mice to Thirdhand Smoke Modulates In Vitro and In Vivo Platelet Responses.

Smoking is a risk factor for a variety of deleterious conditions, such as cancer, respiratory disease and cardiovascular disease. Thrombosis is an important and common aspect of several cardiovascular disease states, whose risk is known to be increased by both first- and secondhand smoke. More recently, the residual cigarette smoke that persists after someone has smoked (referred to as thirdhand smoke or THS) has been gaining more attention, since it has been shown that it also negatively affects health. Indeed, we have previously shown that 6-month exposure to THS increases the risk of thrombogenesis. However, neither the time-dependence of THS-induced thrombus formation, nor its sex dependence have been investigated. Thus, in the present study, we investigated these issues in the context of a shorter exposure to THS, specifically 3 months, in male and female mice. We show that the platelets from 3-month THS-exposed mice exhibited enhanced activation by agonists. Moreover, we also show that mice of both sexes exposed to THS have decreased tail bleeding as well as decreased thrombus occlusion time. In terms of the role of sex, intersex disparities in thrombus development and hemostasis as well as in platelet aggregation were, interestingly, observed. Together, our findings show that exposing mice to THS for 3 months is sufficient to predispose them to thrombosis; which seems to be driven, at least in part, by an increased activity in platelets, and that it does not manifest equally in both sexes.