Bakgrund: Hjärt-kärlsjukdom är den största dödsorsaken globalt och den vanligaste dödsorsaken hos både kvinnor och män i Sverige. Primärvården och således distriktssköterskan har en viktig funktion när det gäller att arbeta förebyggande med hjärt-kärlsjukdom, och med ett hälsofrämjande synsätt utgöra ett stöd för alla människor oavsett ålder, bakgrund och sjukdom. Syfte: Syftet med studien var att beskriva distriktssköterskors och sjuksköterskors erfarenheter av att arbeta förebyggande med hjärt-kärlsjukdom inom primärvården. Metod: Studien hade en deskriptiv design med en kvalitativ ansats. Data har samlats in genom semistrukturerade intervjuer utifrån en sammanställd intervjuguide med öppna frågor. Totalt deltog åtta distriktssköterskor och en sjuksköterska som arbetade inom primärvården. Huvudresultat: I studien framkom att deltagarna upplevde det förebyggande arbetet som väldigt viktigt samtidigt som det var utmanande och begränsades av olika hinder och skillnader i förutsättningar. Deltagarna beskrev att innebörden att arbeta förebyggande med hjärt-kärlsjukdom handlade om att identifiera levnadsvanor, samtala om livsstilsförändring, motivera till livsstilsförändring samt följa patienter över tid och hålla koll på deras parametrar och prover. Deltagarna beskrev vidare att de mest fördelaktiga förutsättningar att arbeta förebyggande fanns om arbetet skedde på en specialistmottagning, såsom en diabetes- eller hypertonimottagning där det fanns mer tid samt möjlighet att lägga upp arbetet mer fritt. Slutsats: Deltagarna i föreliggande studie beskrev det förebyggande arbetet som viktigt men utmanande. Hinder i det förebyggande arbetet beskrevs som tids- och resursbrist samt kunskapsbrist. Föreliggande studie kan bidra genom att belysa distriktssköterskors erfarenheter av att arbeta förebyggande med hjärt-kärlsjukdom och på sikt förbättra deras förutsättningar. / Background: Cardiovascular disease is the biggest cause of death globally and the most common cause of death in both women and men in Sweden. Primary care and thus the primary health care nurse have an important function when it comes to health prevention work with cardiovascular disease, and with a health-promoting approach provide support for all people regardless of age, background and illness. Purpose: The purpose of this study was to describe the primary health care nurses' and nurses` experiences of health prevention work with cardiovascular disease in primary care. Method: The study had a descriptive design with a qualitative approach. Data has been collected through semi-structured interviews based on a compiled interview guide with open questions. A total of eight primary health care nurses and one nurse who worked in primary care participated. Main findings: The study showed that the participants felt that it was very important to work with health prevention, at the same time as it was challenging and limited by various obstacles and differences in conditions. The participants described that the meaning of health prevention work with cardiovascular disease was about identifying lifestyle habits, talking about lifestyle change, motivating lifestyle change and following patients over time and keeping track of their parameters and samples. The participants further described the most favourable conditions for working with health prevention were if the work took place in a specialist reception, such as a diabetes- or hypertension reception where there was more time and the opportunity to schedule the work more freely. Conclusion: The participants in the present study described that working with health prevention was important but challenging. Obstacles in working with health prevention were described as lack of time and resources as well as a lack of knowledge. The present study can contribute by highlighting the experiences of primary health care nurses`  and nurses in health prevention work with cardiovascular disease and in the long term improving their conditions.

A Calibrated Cuff Plethysmography device was built, tested for verification, and used to experiment on human subjects to measure the cardiovascular response of consuming a beet supplement, specifically looking at arterial compliance and pressure-area curves. Each subject was tested four times. A baseline was measured under normal conditions and after five-minute hyperemia conditions. 10 subjects were given 6 ounces of water mixed with either purple Kool-Aid (control), a SuperBeets supplement, or a SuperBeets Sport supplement and after 45 minutes, measurements were taken undergoing normal and hyperemia conditions once more. The verification testing demonstrated the calibration of the device was effectively able to measure volume changes using a stationary metal pipe and IV bag, showing an average percent error of 3.11%. Data collected during the patient experiment resulted in the expected arterial compliance curves as well as pressure-area curves, when measurements were taken properly, and the subject didn’t move. These tests were able to validate the use of the device for measuring arterial compliance and seeing distinctions between normal and hyperemic conditions. However, many issues were presented and are thoroughly addressed in this paper for future research using the same device.

In the field of gerontology, there is a question regarding whether certain diseases can accelerate the progression of other diseases. Given that there is no existing cure for dementia, there is an undeniable upsurge in demand for research concerning identifying preventive measures that influence the onset or development of cognitive decline. Cerebral atherosclerosis is characterized by the thickening of artery walls within the brain. Many studies have shifted their focus on examining the role nutrients and food play in preventing cognitive decline, dementia, cerebral atherosclerosis, and Alzheimer’s disease (AD). This thesis provides a comprehensive overview of existing observational and clinical trial evidence published up to date for the association of dietary intervention between cognitive health, dementia, AD, and cerebral atherosclerosis.

Despite the advent of stents, intimal hyperplasia subsequent to vascular interventional procedures remains a major obstacle. Vascular smooth muscle cells (VSMC) play a critical role in the pathogenesis of intimal hyperplasia; therefore, regulation of VSMC gene expression is a logical intervention point. FXR1 is a muscle-enhanced RNA binding protein and its expression is increased in injured arteries. We have shown that modulation of FXR1 levels affects stability and abundance of inflammatory transcripts in VSMC, suggesting that FXR1 is a negative regulator of inflammation. RNA-sequencing analysis in FXR1-depleted human VSMC (hVSMC) identified a number of transcripts with decreased abundance, the overwhelming majority of which were associated with proliferation and cell division. This drives our hypothesis that FXR1 is involved in mitigating vascular disease by regulating inflammatory and proliferative mRNA in VSMC. The mRNA abundance and stability of a number of these transcripts was decreased in FXR1 depleted hVSMC, and RIP-sequencing demonstrated that FXR1 interacts with transcripts involved in cell cycle control, and stability of these transcripts is decreased with FXR1 depletion. FXR1-depleted cells showed decreased proliferation (p<0.05), however, an increase in β-galactosidase (p<0.05) and γH2AX (p<0.01), indicative of senescence was noted. Senescent cells exhibit a senescence associated secretory phenotype (SASP) with characteristic gene expression leading to increased inflammation in the tissue microenvironment. HVSMC depleted of FXR1 had increased transcripts abundance of many SASP genes, as well as an increase of both mRNA and protein expression of canonical senescence markers p53 and p21. We developed a novel SMC-specific conditional knockout mouse (FXR1SMC/SMC) to further study these results in a more translational context. In a carotid artery ligation model of intimal hyperplasia, FXR1SMC/SMC mice have significantly reduced neointima formation (p<0.001) post-ligation compared to controls. qPCR analysis from FXR1 conditional knockout mouse VSMC (mVSMC) show increased transcripts associated with senescence (p21, p16, p53) as well as increased SASP-associated mRNA, a decrease in proliferation, and an increase in β-galactosidase staining. Our results are the first to suggest that in addition to destabilization of inflammatory transcripts, FXR1 may stabilize cell cycle related genes in VSMC, and absence of FXR1 leads to induction of a senescent phenotype, an increase in SASP genes, and reduction of intimal hyperplasia. / Organ Systems & Translational Medicine

Chronic kidney disease (CKD) is growing global public health problem affecting 1 in 10 adults in developed countries and recognised as an important risk factor for cardiovascular disease (CVD) development. CVD is the main cause of death among CKD patients. Endothelial injury and dysfunction are critical steps in atherosclerosis, a major CVD. Oxidative stress (increased level of reactive oxygen species, ROS) has been associated with CVD development. Intravenous (IV) iron preparations are widely used in the management of CKD mediated anaemia, and have been associated with increased oxidative stress and cellular dysfunction. This study examined the effect of pharmacologically-relevant concentrations of IV Venofer (iron sucrose) or IV Ferinject (Ferric carboxymaltose, FCM) on primary human umbilical vein endothelial cell (HUVEC) activation/damage and on intracellular ROS generation as well as studying the potential mechanisms responsible. Data from TUNEL assay and Annexin V-FITC/PI staining showed that, IV FCM had no effect, but IV iron sucrose increased HUVEC apoptosis at 24hr. IV iron sucrose inhibited cell proliferation and reduced cell viability. Both compounds induced EC activation through sustained activation of p38 MAPK and up-regulation of ICAM-1 and VCAM-1. Additionally, the compounds induced significant increase in total ROS and superoxide anion production, which was attenuated by the anti-oxidant N-acetylcysteine (NAC). P38 MAPK showed up-regulation of pro-apoptotic protein Bax and down-regulation of antiapoptotic Bcl-2 protein in HUVEC treated with IV iron sucrose and p38 inhibition reversed these effects. In summary, these results suggest that IV iron sucrose causes more severe EC injury than IV FCM. However, both IV iron preparations induced intracellular ROS and superoxide anion generation in HUVEC leading to EC activation/dysfunction, providing a potential explanation for vascular damage in CKD patients.

Psoriasis is an immune mediated inflammatory disease which affects 2-3% of the world’s population. Over the last decade, psoriasis has been acknowledged as an independent risk factor for atherosclerosis. The precise mechanism or mechanisms of the heightened risk is widely speculated. Endothelial cells and macrophages are central players in the immunopathological development of both diseases. Interleukin-36 cytokines (IL-36) have been heavily implicated in psoriasis immunopathology. Significant upregulation of epidermal IL-36 is a recognised characteristic of psoriatic skin inflammation. IL-36 induces inflammatory responses in dendritic cells, fibroblasts and epithelial cells. While vascular alterations are a hallmark of psoriatic lesions and dermal endothelial cells are well known to play a critical role in dermal inflammation, the effects of IL-36 on endothelial cells have not been defined. We report that endothelial cells including dermal microvascular cells express a functionally active IL-36 receptor. Adhesion molecules VCAM-1 and ICAM-1 are upregulated following IL-36γ stimulation, and this is reversed in the presence of the endogenous IL-36 receptor antagonist. IL-36γ-stimulated endothelial cells secrete the proinflammatory chemokines IL-8, CCL2 and CCL20. Chemotaxis assays showed increased migration of T-cells following IL-36γ stimulation of endothelial cells. Both resident and infiltrating inflammatory myeloid cells contribute to the immunopathology of psoriasis by promoting the IL-23/IL-17 axis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23, TNFα) and that this response is enhanced in macrophages from psoriasis patients. This effect is specific for IL-36γ and could not be mimicked by other IL-1 family cytokines such as IL-1α. Furthermore, IL-36γ stimulated macrophages potently activated endothelial cells as illustrated by ICAM-1(CD54) upregulation, and led to increased adherence of monocytes, effects that were markedly more pronounced for psoriatic macrophages. Interestingly, regardless of stimulus, monocytes isolated from psoriasis patients showed increased adherence to both the stimulated and unstimulated endothelium when compared to monocytes from healthy individuals. Collectively, these findings add to the growing evidence for IL-36γ having roles in psoriatic responses, by enhancing endothelium directed leukocyte infiltration into the skin and strengthening the IL-23/IL-17 pathway. Our findings also point to a cellular response which could potentially support cardiovascular comorbidities in psoriasis. / University of Bradford and the Centre for Skin Sciences

While the adverse health risks associated with smoking have been well-documented, few studies have examined the cardiovascular outcomes associated with secondhand smoking. The purpose of the study was to assess the distributions and association of cardiovascular diseases (CVDs) in nonsmokers exposed to secondhand smoke (SHS). Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 cycle. Self-reported smoking status and cotinine levels were used to identify exposure groups (smokers, nonsmokers, and secondhand smokers), and medical history of several cardiovascular diseases such as coronary heart diseases and stroke were also collected via self-report survey. The association between exposure to SHS and seven cardiovascular outcomes were analyzed using chi-square analysis and odd ratios (OR) with 95% confidence intervals (CIs) were calculated using two logistic regression models. The data included 5,709 subjects including 18.5% smokers, 23.6% secondhand smokers, and 57.9% nonsmokers. There was statistically significant association between exposure to SHS and only two out of seven cardiovascular outcomes, hypertension (OR 1.554, 95% CI [1.066, 2.265]) and cholesterol levels (OR 1.213, 95% CI [1.017, 1.446]). This study is one of the first to determine an association between SHS and seven cardiovascular outcomes, thus highlighting the importance of reducing SHS exposure and can be used for further research on SHS and cardiovascular health.

Food insecurity is a growing issue in the United States. Iron deficiency is the most common form of nutritional deficiency in patients with endothelial dysfunction and vascular-related diseases. This preliminary study lays the groundwork for the “Nutrient deficiency-on-a-chip” model. Endothelial cells are cultured on mechanically tunable, enzymatically cross-linked gelatin and treated with deferoxamine, an iron chelator, or angiotensin II were used to simulate a nutrient deficient and diseased environment, respectively. As oxidative stress and disturbed barrier function are the most prevailing mechanism of angiotensin II and iron deficiency induced endothelial dysfunction, to test our model we investigated the changes in reactive oxygen species production and VE-cadherin expression in engineered endothelium. Both angiotensin II and deferoxamine treated engineered endothelium showed an increase in oxidative stress and disturbed barrier function. This in vitro model can be a useful tool to better understand disease mechanisms associated with nutrient deficiency and identify novel therapeutics.

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