The impact of air quality on cardiovascular health: A state of the art review.

Air pollution is a global health challenge, increasing the risk of cardiovascular diseases such as heart disease, stroke, and arrhythmias. Particulate matter (PM), particularly PM2.5 and ultrafine particles (UFP), is a key contributor to the adverse effects of air pollution on cardiovascular health. PM exposure can lead to oxidative stress, inflammation, atherosclerosis, vascular dysfunction, cardiac arrhythmias, and myocardial injury. Reactive oxygen species (ROS) play a key role in mediating these effects. PM exposure can also lead to hypertension, a significant risk factor for cardiovascular disease. The COVID-19 pandemic resulted in a significant reduction of air pollutants, leading to a decline in the incidence of heart attacks and premature deaths caused by cardiovascular diseases. This review highlights the relationship between environmental air quality and cardiovascular health, elucidating the pathways through which air pollutants affect the cardiovascular system. It also emphasizes the need for increased awareness, collective efforts to mitigate the adverse effects of air pollution, and strategic policies for long-term air quality improvement to prevent the devastating effects of air pollution on global cardiovascular health.

The synergistic effect of high temperature and ozone on the number of deaths from circulatory system diseases in Shijiazhuang, China.

Introduction: Urban ozone pollution in China is becoming increasingly serious. Climate warming, high temperatures, and ozone pollution all have significant impacts on human health. However, the synergistic effects of high temperatures and ozone pollution in summer on human health are rarely studied. China is at a critical stage of environmental pollution control. Assessing the health impact of high temperatures and ozone exposure on the number of deaths from circulatory diseases is of great significance for formulating ozone-related prevention and control policies. Methods: This study uses daily data on deaths from circulatory system diseases in Shijiazhuang from June to August during the summer of 2013-2016, as well as concurrent meteorological data and concentration of O3 and PM2.5 pollution data. The generalized additive model (GAM) with Poisson distribution, smooth curve threshold effect, and saturation effect method is used to control for confounding effects. Results: The study evaluates the impact of short-term exposure to temperature and ozone on deaths from circulatory system diseases and the synergistic effect after controlling for confounding factors. The results show that the impact of temperature and ozone on deaths from circulatory system diseases in Shijiazhuang is nonlinear, with a temperature threshold of 27.5°C and an ozone concentration threshold of 100 µg/m3. With an increase of temperature by 1°C, the risk of deaths for total population, men and women are 6.8%, 4.6% and 9.3%, respectively. The increase in temperature and ozone concentration has a greater impact on women; in men, the increase has a lag effect of 2 to 3 days, but the lag did not affect women. Discussion: In conclusion, high temperatures and high ozone concentration have synergistic enhancement effects on circulatory system diseases. Prevention and scientific management strategies of circulatory system diseases in high temperatures and high ozone environments should be strengthened.

Acute exposure of Isopyrazam damages the developed cardiovascular system of zebrafish (Danio rerio).

Isopyrazam (IPZ) is one of the broad-spectrum succinate dehydrogenase inhibitor fungicides (SDHIs). Although the potential bio-toxicity of SDHIs has been reported hourly, the specific effects focused on the cardiovascular system have remained unclear and piecemeal. Thus, we chose IPZ as a representative to observe the cardiovascular toxicity of SDHIs in zebrafish. Two types of transgenic zebrafish, Tg (cmlc2:GFP) and Tg (flk1:GFP) were used in this study. Healthy embryos at 6 hpf were exposed to IPZ solutions. The statistical data including survival rate, hatching rate, malformed rate, and morphological and functional parameters of the cardiovascular system at 48 hpf and 72 hpf demonstrated that IPZ could cause abnormalities and cardiovascular defects such as spinal curvature, dysmotility, pericardial edema, pericardial hemorrhage, and slowed heart rate, etc. At the same time, the activity of enzymes related to oxidative stress was altered with IPZ. Our results revealed that IPZ-induced cardiovascular toxicity and oxidative stress might be one of the underlying toxic mechanisms.

Associations between short-term PM2.5 exposure and daily hospital admissions for circulatory system diseases in Ganzhou, China: A time series study.

Objective: Previous epidemiological studies have shown that both long-term and short-term exposure to fine particulate matters (PM2.5) were associated with the morbidity and mortality of circulatory system diseases (CSD). However, the impact of PM2.5 on CSD remains inconclusive. This study aimed to investigate the associations between PM2.5 and circulatory system diseases in Ganzhou. Methods: We conducted this time series study to explore the association between ambient PM2.5 exposure and daily hospital admissions for CSD from 2016 to 2020 in Ganzhou by using generalized additive models (GAMs). Stratified analyses were also performed by gender, age, and season. Results: Based on 201,799 hospitalized cases, significant and positive associations were found between short-term PM2.5 exposure and hospital admissions for CSD, including total CSD, hypertension, coronary heart disease (CHD), cerebrovascular disease (CEVD), heart failure (HF), and arrhythmia. Each 10 µg/m3 increase in PM2.5 concentrations was associated with a 2.588% (95% confidence interval [CI], 1.161%-4.035%), 2.773% (95% CI, 1.246%-4.324%), 2.865% (95% CI, 0.786%-4.893%), 1.691% (95% CI, 0.239%-3.165%), 4.173% (95% CI, 1.988%-6.404%) and 1.496% (95% CI, 0.030%-2.983%) increment in hospitalizations for total CSD, hypertension, CHD, CEVD, HF, and arrhythmia, respectively. As PM2.5 concentrations rise, the hospitalizations for arrhythmia showed a slow upward trend, while other CSD increased sharply at high PM2.5 levels. In subgroup analyses, the impacts of PM2.5 on hospitalizations for CSD were not materially changed, although the females had higher risks of hypertension, HF, and arrhythmia. The relationships between PM2.5 exposure and hospitalizations for CSD were more significant among individuals aged ≤65 years, except for arrhythmia. PM2.5 had stronger effects on total CSD, hypertension, CEVD, HF, and arrhythmia during cold seasons. Conclusion: PM2.5 exposure was positively associated with daily hospital admissions for CSD, which might provide informative insight on adverse effects of PM2.5.

Time series analysis of short-term effects of particulate matter pollution on the circulatory system disease mortality risk in Lishui District, China.

Epidemiological evidence has shown a significant association between short-term exposure to air pollution and mortality risk for circulatory system diseases (CSD). However, informative insights on the significance and magnitude of its relationship in the process of government interventions on abating air pollution are still lacking, particularly in a burgeoning Chinese city. In this study, we conducted a time series study in Lishui District, Nanjing, to examine the effect of ambient particulate matter (PM), e.g., PM2.5 and PM10, on daily death counts of CSD which included cardiovascular disease (CVD), cerebrovascular disease (CEVD), and arteriosclerotic heart disease (ASHD) mortality from January 1, 2015, to December 31, 2019. The results revealed that each 10 µg/m3 increase in PM2.5 and PM10 concentration at lag0 day was associated with an increase of 1.33% (95% confidence interval, 0.08%, 2.60%) and 1.12% (0.43%, 1.82%) in CSD mortality; 2.42% (0.44%, 4.43%) and 1.43% (0.32%, 2.55%) in CVD mortality; 1.20% (- 0.31%, 2.73%) and 1.21% (0.38%, 2.05%) in CEVD mortality; and 2.78% (0.00%, 5.62%) and 1.66% (0.14%, 3.21%) in ASHD mortality, respectively. For cumulative risk, the corresponding increase in daily mortality for the same change in PM2.5 concentration at lag03 day was significantly associated with 1.94% (0.23%, 3.68%), 3.17% (0.58%, 5.84%), 2.38% (0.17%, 4.63%), and 4.92% (1.18%, 8.81%) for CSD, CVD, CEVD, and ASHD, respectively. The exposure-response curves were approximately nonlinear over the entire exposure range of the PM concentrations. We also analyzed the effect modifications by season (warm or cold), age group (0-64 years, 65-74 years, or ≥ 75 years), and sex (male or female). Although not statistically significant, stratified analysis showed greater vulnerability to PM exposure for cold season, population over 65 years of age, and female group.

Role of whey protein in vascular function: a systematic review and meta-analysis of human intervention studies.

Whey protein (WP) has been heavily appreciated as a rich source of bioactive peptides, with potential benefits for cardiovascular health. This study constitutes a systematic review and meta-analysis summarising the effects of WP consumption on vascular reactivity, arterial stiffness and circulatory biomarkers of vascular function. We searched electronic databases, including PubMed, SCOPUS and Web of science for relevant articles from inception to July 2020. Original clinical trials published in English-language journals that investigated the effects of WP on vascular function were eligible. A total of 720 records were identified in the initial search; from these, sixteen were included in our systematic review and thirteen in meta-analysis. The pooled analysis of six studies showed a significant increase in flow-mediated dilation (FMD) after WP consumption (weighted mean differences (WMD): 1·09 %, 95 % CI: 0·17, 2·01, P= 0·01). Meta-analysis of available data did not show any significant reduction in arterial stiffness measures including augmentation index (effect sizes: 7, WMD: -0·29 %, 95 % CI: -1·58, 0·98, P= 0·64) and pulse wave velocity (effect sizes: 4, WMD: -0·72 m/s, 95 % CI: -1·47, 0·03, P= 0·06). Moreover, the pooled analysis of six effect sizes showed no significant effects on plasma levels of nitric oxide following WP supplementation (WMD: 0·42 µmol/l, 95 % CI: -0·52, 1·36, P= 0·38). The overall results provided evidence supporting a protective effect of WP on endothelial function measured by FMD, but not for arterial stiffness measures and circulatory biomarker of vascular function. Further research is required to substantiate the benefits of WP on vascular function.

Immuno-regenerative biomaterials for in situ cardiovascular tissue engineering - Do patient characteristics warrant precision engineering?

In situ tissue engineering using bioresorbable material implants - or scaffolds - that harness the patient's immune response while guiding neotissue formation at the site of implantation is emerging as a novel therapy to regenerate human tissues. For the cardiovascular system, the use of such implants, like blood vessels and heart valves, is gradually entering the stage of clinical translation. This opens up the question if and to what extent patient characteristics influence tissue outcomes, necessitating the precision engineering of scaffolds to guide patient-specific neo-tissue formation. Because of the current scarcity of human in vivo data, herein we review and evaluate in vitro and preclinical investigations to predict the potential role of patient-specific parameters like sex, age, ethnicity, hemodynamics, and a multifactorial disease profile, with special emphasis on their contribution to the inflammation-driven processes of in situ tissue engineering. We conclude that patient-specific conditions have a strong impact on key aspects of in situ cardiovascular tissue engineering, including inflammation, hemodynamic conditions, scaffold resorption, and tissue remodeling capacity, suggesting that a tailored approach may be required to engineer immuno-regenerative biomaterials for safe and predictive clinical applicability.

Effect of welding fumes on the cardiovascular system: a six-year longitudinal study.

Objective This study investigated whether low-to-moderate exposure to welding fumes is associated with adverse effects on the cardiovascular system. Methods To test this, we performed a longitudinal analysis of 78 mild steel welders and 96 controls; these subjects were examined twice, six years apart (ie, timepoints 1 and 2). All subjects (male and non-smoking at recruitment) completed questionnaires describing their health, work history, and lifestyle. We measured their blood pressure, endothelial function (by EndoPAT), and risk markers for cardiovascular disease [low-density lioprotein (LDL), homocysteine, C-reactive protein]. Exposure to welding fumes was assessed from the responses to questionnaires and measurements of respirable dust in their breathing zones adjusted for use of respiratory protection equipment. Linear mixed-effect regression models were used for the longitudinal analysis. Results Median respirable dust concentrations, adjusted for respirable protection, of the welders were 0.7 (5-95 percentile range 0.2-4.2) and 0.5 (0.1-1.9) mg/m 3at timepoints 1 and 2, respectively. Over the six-year period, welders showed a statistically significant increase in systolic [5.11 mm Hg, 95% confidence interval (CI) 1.92-8.31] and diastolic (3.12 mm Hg, 95% CI 0.74-5.5) blood pressure compared with controls (multi-variable adjusted mixed effect models). Diastolic blood pressure increased non-significantly by 0.22 mm Hg (95% CI -0.02-0.45) with every additional year of welding work. No consistent significant associations were found between exposure and endothelial function, LDL, homocysteine, or C-reactive protein. Conclusion Exposure to welding fumes at low-to-moderate levels is associated with increased blood pressure, suggesting that reducing the occupational exposure limit (2.5 mg/m 3for inorganic respirable dust in Sweden) is needed to protect cardiovascular health of workers.

Healthy cardiovascular biomarkers across the lifespan in wild-born chimpanzees (Pan troglodytes).

Chimpanzees (Pan troglodytes) are a crucial model for understanding the evolution of human health and longevity. Cardiovascular disease is a major source of mortality during ageing in humans and therefore a key issue for comparative research. Current data indicate that compared to humans, chimpanzees have proatherogenic blood lipid profiles, an important risk factor for cardiovascular disease in humans. However, most work to date on chimpanzee lipids come from laboratory-living populations where lifestyles diverge from a wild context. Here, we examined cardiovascular profiles in chimpanzees living in African sanctuaries, who range semi-free in large forested enclosures, consume a naturalistic diet, and generally experience conditions more similar to a wild chimpanzee lifestyle. We measured blood lipids, body weight and body fat in 75 sanctuary chimpanzees and compared them to publicly available data from laboratory-living chimpanzees from the Primate Aging Database. We found that semi-free-ranging chimpanzees exhibited lower body weight and lower levels of lipids that are risk factors for human cardiovascular disease, and that some of these disparities increased with age. Our findings support the hypothesis that lifestyle can shape health indices in chimpanzees, similar to effects observed across human populations, and contribute to an emerging understanding of human cardiovascular health in an evolutionary context. This article is part of the theme issue 'Evolution of the primate ageing process'.

Exploring the Benefit of 2-Methylbutyric Acid in Patients Undergoing Hemodialysis Using a Cardiovascular Proteomics Approach.

Short-chain fatty acids (SCFAs) can reduce pro-inflammatory parameters and oxidative stress, providing potential cardiovascular (CV) benefits. Although some evidence links SCFAs with host metabolic health via several biological mechanisms, the role of SCFA on CV disease in patients with kidney disease remains unclear. Herein, we investigate the association between a SCFA, 2-methylbutyric acid, and target CV proteomics to explore the potential pathophysiology of SCFA-related CV benefit in patients with kidney disease. Circulating 2-methylbutyric acid was quantified by high-performance liquid chromatography and 181 CV proteins by a proximity extension assay in 163 patients undergoing hemodialysis (HD). The associations between 2-methylbutyric acid and CV proteins were evaluated using linear regression analysis with age and gender, and multiple testing adjustment. The selected CV protein in the discovery phase was further confirmed in multivariable-adjusted models and evaluated by continuous scale association. The mean value of circulating 2-methylbutyric acid was 0.22 ± 0.02 µM, which was negatively associated with bone morphogenetic protein 6 (BMP-6) according to the false discovery rate (FDR) multiple testing adjustment method. The 2-methylbutyric acid level remained negatively associated with BMP-6 (ß coefficient -1.00, 95% confidence interval -1.45 to -0.55, p < 0.001) after controlling for other CV risk factors in multivariable models. The cubic spline curve demonstrated a linear relationship. In conclusion, circulating 2-methylbutyric acid level was negatively associated with BMP-6, suggesting that this pathway maybe involved in vascular health in patients undergoing HD. However, further in vitro work is still needed to validate the translation of the mechanistic pathways.

Physicochemical characterization of human cardiovascular deposits.

Detailed crystal chemical characterization of human pathological cardiovascular deposits (PCD) was conducted applying wide set of the instrumental methods (XRD, FTIR, Raman, SEM, different chemical analyses). There was some progress achieved in the understanding of it formation mechanism. The obtained data evidence that pathological cardiovascular deposits are presented by non-stoichiometric water-bearing B-type carbonated hydroxyapatite just like other apatites of the human body. But PCD apatite is characterized by higher concentration of B-type carbonate ion (up to ~ 6 wt%) which leads to the increasing influence of the carbonate-ion on the unit cell parameters in comparison with water and other substitutes. Another difference between PCD apatite and other pathogenic apatites of the human body is the smaller variations of the unit cell parameters, caused by smaller variations of the blood chemical composition. It was shown that apatite on the surface of PCD is characterized by the more non-stoichiometric composition compared to apatite inside these deposits. It is assumed that the formation mechanisms of the PCD apatite and the bone apatite may be similar.

An evaluation of microalgae as a recombinant protein oral delivery platform for fish using green fluorescent protein (GFP).

Recombinant proteins produced by biological systems such as bacteria, yeasts, mammalian and insect cell cultures are widely used for clinical or industrial purposes. Most therapeutic protein drugs require purification, cold chain, and injection, which make them prohibitively expensive and hinders their widespread use. Here, we describe a new economical oral vaccination platform using algae and evaluated its potential for the delivery of recombinant drugs using GFP expressed in the chloroplast of algal cells. The transplastomic algae expressing recombinant GFPs were freeze-dried for long-term storage at ambient temperature and for easy handling in feeding. GFPs bioencapsulated by lyophilized Chlamydomonas reinhardtii were found intact without degradation for several months at ambient temperature. The expression level of GFP in the lyophilized algae was estimated at 0.47 µg/mg dry weight. The GFPs bioencapsulated and orally delivered to Danio rerio were immunostained and observed in the intestinal tissues using a confocal microscope. Furthermore, the uptaken GFPs in the intestine were detected in the blood using ELISA and the detected level was 5.4 ng of GFP/µl of serum. These results demonstrate that microalgae can be a viable protein production and oral delivery system to vaccinate fish. The results give greater justification to continue exploring the concept of microalgal-based oral vaccines. The potential of the technology would greatly benefit aquaculture farmers by providing them with affordable, environmentally sustainable, and user-friendly vaccines.

Corticotropin-Releasing Hormone Family and Their Receptors in the Cardiovascular System.

The identification of corticotropin-releasing hormone (CRH) has led to the discovery of a growing family of ligands and receptors. CRH receptor 1 (CRHR1) and CRHR2 are mammalian G-protein coupled receptors (GPCRs) with high affinity for CRH and the CRH family of peptides. CRHR1 is predominantly expressed in the brain and plays a vital role in the hypothalamic-pituitary-adrenal (HPA) axis stress responses by secreting adrenal corticotropic hormone (ACTH). CRHR2 is predominantly expressed in the heart, and a CRHR2-specific ligand, urocortin 2 (UCN2), shows positive cardiac chronotropic and inotropic effects through 3´,5´-cyclic adenosine monophosphate (cAMP) signaling in response to CRHR2-mediated Gαs activation in mice and humans. Central administration of the CRH family of peptides increases mean arterial pressure through CRHR1 activation, whereas peripheral administration of the peptides decreases mean arterial pressure through CRHR2 activation. These observations have led to further investigations of CRHR2 as an important and unique GPCR in the physiological and pathological functioning of the cardiovascular (CV) system. Moreover, recent clinical trials demonstrate CRHR2 as a potentially therapeutic target in the treatment of heart failure. We present recent reviews of the role of CRHRs in basic CV physiology and in the pathophysiology of CV diseases.

Measurement of Reactive Oxygen Species, Reactive Nitrogen Species, and Redox-Dependent Signaling in the Cardiovascular System: A Scientific Statement From the American Heart Association.

Reactive oxygen species and reactive nitrogen species are biological molecules that play important roles in cardiovascular physiology and contribute to disease initiation, progression, and severity. Because of their ephemeral nature and rapid reactivity, these species are difficult to measure directly with high accuracy and precision. In this statement, we review current methods for measuring these species and the secondary products they generate and suggest approaches for measuring redox status, oxidative stress, and the production of individual reactive oxygen and nitrogen species. We discuss the strengths and limitations of different methods and the relative specificity and suitability of these methods for measuring the concentrations of reactive oxygen and reactive nitrogen species in cells, tissues, and biological fluids. We provide specific guidelines, through expert opinion, for choosing reliable and reproducible assays for different experimental and clinical situations. These guidelines are intended to help investigators and clinical researchers avoid experimental error and ensure high-quality measurements of these important biological species.

Data-Driven Approach To Determine Popular Proteins for Targeted Proteomics Translation of Six Organ Systems.

Amidst the proteomes of human tissues lie subsets of proteins that are closely involved in conserved pathophysiological processes. Much of biomedical research concerns interrogating disease signature proteins and defining their roles in disease mechanisms. With advances in proteomics technologies, it is now feasible to develop targeted proteomics assays that can accurately quantify protein abundance as well as their post-translational modifications; however, with rapidly accumulating number of studies implicating proteins in diseases, current resources are insufficient to target every protein without judiciously prioritizing the proteins with high significance and impact for assay development. We describe here a data science method to prioritize and expedite assay development on high-impact proteins across research fields by leveraging the biomedical literature record to rank and normalize proteins that are popularly and preferentially published by biomedical researchers. We demonstrate this method by finding priority proteins across six major physiological systems (cardiovascular, cerebral, hepatic, renal, pulmonary, and intestinal). The described method is data-driven and builds upon the collective knowledge of previous publications referenced on PubMed to lend objectivity to target selection. The method and resulting popular protein lists may also be useful for exploring biological processes associated with various physiological systems and research topics, in addition to benefiting ongoing efforts to facilitate the broad translation of proteomics technologies.

Transgenic mice for cGMP imaging.

RATIONALE: Cyclic GMP (cGMP) is an important intracellular signaling molecule in the cardiovascular system, but its spatiotemporal dynamics in vivo is largely unknown. OBJECTIVE: To generate and characterize transgenic mice expressing the fluorescence resonance energy transfer-based ratiometric cGMP sensor, cGMP indicator with an EC50 of 500 nmol/L (cGi500), in cardiovascular tissues. METHODS AND RESULTS: Mouse lines with smooth muscle-specific or ubiquitous expression of cGi500 were generated by random transgenesis using an SM22α promoter fragment or by targeted integration of a Cre recombinase-activatable expression cassette driven by the cytomegalovirus early enhancer/chicken ß-actin/ß-globin promoter into the Rosa26 locus, respectively. Primary smooth muscle cells isolated from aorta, bladder, and colon of cGi500 mice showed strong sensor fluorescence. Basal cGMP concentrations were < 100 nmol/L, whereas stimulation with cGMP-elevating agents such as 2-(N,N-diethylamino)-diazenolate-2-oxide diethylammonium salt (DEA/NO) or the natriuretic peptides, atrial natriuretic peptide, and C-type natriuretic peptide evoked fluorescence resonance energy transfer changes corresponding to cGMP peak concentrations of ≈ 3 µmol/L. However, different types of smooth muscle cells had different sensitivities of their cGMP responses to DEA/NO, atrial natriuretic peptide, and C-type natriuretic peptide. Robust nitric oxide-induced cGMP transients with peak concentrations of ≈ 1 to > 3 µmol/L could also be monitored in blood vessels of the isolated retina and in the cremaster microcirculation of anesthetized mice. Moreover, with the use of a dorsal skinfold chamber model and multiphoton fluorescence resonance energy transfer microscopy, nitric oxide-stimulated vascular cGMP signals associated with vasodilation were detected in vivo in an acutely untouched preparation. CONCLUSIONS: These cGi500 transgenic mice permit the visualization of cardiovascular cGMP signals in live cells, tissues, and mice under normal and pathological conditions or during pharmacotherapy with cGMP-elevating drugs.

HUPO 2011: The new Cardiovascular Initiative - integrating proteomics and cardiovascular biology in health and disease.

A newly reorganized HUPO Cardiovascular Initiative was announced at the HUPO 2011 Cardiovascular Initiative Workshop at Geneva. The new initiative is now part of the biology- and disease-driven component of the HUPO Human Proteome Project (B/D-HPP). Here we report the recent achievements and future directions of the initiative, and offer a perspective on the present challenges of cardiovascular proteomics and its integration with the cardiovascular biology community at large.

Comparative mitochondrial proteomics: perspective in human diseases.

Mitochondria are the most complex and the most important organelles of eukaryotic cells, which are involved in many cellular processes, including energy metabolism, apoptosis, and aging. And mitochondria have been identified as the "hot spot" by researchers for exploring relevant associated dysfunctions in many fields. The emergence of comparative proteomics enables us to have a close look at the mitochondrial proteome in a comprehensive and effective manner under various conditions and cellular circumstances. Two-dimensional electrophoresis combined with mass spectrometry is still the most popular techniques to study comparative mitochondrial proteomics. Furthermore, many new techniques, such as ICAT, MudPIT, and SILAC, equip researchers with more flexibilities inselecting proper methods. This article also reviews the recent development of comparative mitochondrial proteomics on diverse human diseases. And the results of mitochondrial proteomics enhance a better understanding of the pathogenesis associated with mitochondria and provide promising therapeutic targets.