Aletta M E Millen

• PhD
• Professor at University of the Witwatersrand

Quercetin is known to reduce blood pressure (BP); however, its acute effects are unclear. We investigated the acute effects of quercetin on BP, aortic mechanical properties and vascular reactivity in female Sprague–Dawley (SD) rats. Hypertension was induced using L‐NAME (40 mg/kg/day). Quercetin (4.5 mg/kg) was administered intravenously. Mechanica...

Neuroinflammation has emerged as a significant contributor in the development of major depressive disorder (MDD). It has been suggested that neuroinflammation may potentially be an underlying mechanism driving several other theories in the pathogenesis of this multifactorial disorder. Despite this, the exact pathophysiology of neuroinflammation ind...

Systemic inflammation contributes to left ventricular (LV) dysfunction, however the role of the NLRP3 inflammasome in LV dysfunction in acute inflammatory conditions is unclear. This study investigated the role of the NLRP3 inflammasome in acute (24 h) cardiac structural and functional changes in vivo and in vitro in lipopolysaccharide (LPS)-induce...

Background MicroRNAs have been implicated in the pathogenesis of cardiovascular disease. However, the contribution of microRNAs remain poorly understood in the context of hypertensive cardiac pathology. Aim We investigated the role of miR-146a-5p, -155-5p, and -29b-5p in the development of cardiac hypertrophy and dysfunction in male and female spo...

Simple Summary Auto-immune disorders, such as rheumatoid arthritis, are characterized by high levels of pro-inflammatory cytokines. Continued exposure to high levels of systemic inflammation has several other health consequences, including negative effects on organs such as the brain. These detrimental effects may result in mood and neurological di...

Using our earlier developed protocol, mass spectrometry imaging of small endogenous peptides (and a selection of small metabolites) can be successfully performed directly in tissue sections of formaldehyde-fixed paraffin-embedded (FFPE) samples, such as those available in Homo sapiens biobanks. In analogy with immunohistochemistry (IHC) which emplo...

In Africa, there is currently a paucity of data on the epidemiology of depression, its treatment and management. The prevalence of depression is severely underestimated, with unique circumstances and societal risk factors associated with depression and its public awareness. Treating and managing depression is confounded by an inaccessibility to eff...

Elevated systemic inflammation contributes to pathogenesis of heart failure with preserved ejection fraction (HFpEF), but molecular mechanisms are poorly understood. Although left ventricular (LV) diastolic dysfunction is the main cause of HFpEF, subclinical systolic dysfunction also contributes. We have previously shown that rats with collagen-ind...

Background Titin phosphorylation contributes to left ventricular (LV) diastolic dysfunction. The independent effects of inflammation on the molecular pathways that regulate titin phosphorylation are unclear. Methods We investigated the effects of collagen-induced inflammation and subsequent tumor necrosis factor-α (TNF-α) inhibition on mRNA expres...

Background Interleukin-6 (IL-6) receptor blockers improve systemic inflammation however, their inconsistent effects on lipid metabolism and drug-induced liver injuries warrant further investigation. This study aimed to determine the effects of IL-6 receptor blocker therapy on lipid metabolism and liver morphology in collagen-induced arthritis. Met...

The holistic training of healthcare professionals as a strategy to build the healthcare system has received considerable attention. As part of training a holistic workforce, it is expected the healthcare professionals be component in management and governance. Financial literacy is low globally and impacts financial decision-making and business man...

Chronic inflammation causes dysregulated expression of microRNAs. Aberrant microRNA expression is associated with endothelial dysfunction. In this study we determined whether TNF-α inhibition impacted the expression of miRNA-146a-5p and miRNA-155-5p, and whether changes in the expression of these miRNAs were related to inflammation-induced changes...

Objective: Estrogen deficiency is associated with left ventricular (LV) dysfunction in postmenopausal women and ovariectomized rats. Whether the relationship between estrogen deficiency and LV dysfunction is independent of cardiovascular disease (CVD) risk factors remains uncertain. This study assessed the effects of short-term and long-term estro...

Objective: To determine the mechanisms of inflammation-induced left ventricular (LV) remodeling and effects of blocking circulating tumor necrosis factor alpha (TNF-α) in a model of systemic inflammation. Methods: Seventy Sprague-Dawley rats were divided into three groups: the control group, the collagen-induced arthritis (CIA) group, and the an...

Objectives: To determine biologic disease-modifying anti-rheumatic drug effects on inflammation-induced cardiac geometry and function changes. Methods: Male and female Sprague-Dawley rats (n=92) were divided into four groups: control group, collagen-induced arthritis (CIA) group, anti-TNF-α group and anti-IL-6 group. Inflammation was induced by...

Mountain biking, unlike road cycling, includes vibrational accelerations but whether it stimulates osteogenic signaling remains unknown. Furthermore, exercise nutrition influences bone turnover, and the effect of ingesting protein during multiday racing was investigated. We measured plasma bone turnover markers, C-terminal telopeptide of type1-coll...

Background High-grade inflammation may play a pivotal role in the pathogenesis of left ventricular (LV) dysfunction. Evidence to support a role of systemic inflammation in mediating impaired LV function in experimental models of rheumatoid arthritis (RA) remains limited. The aim of the present study was to determine the effects of high-grade system...

Background: There is a high prevalence of women in South Africa with overweight and obesity which is associated with an increased risk of cardiometabolic disorders. Perceived barriers such as lack of time and motivation reduce engagement in beneficial activity behaviours for health. High-intensity interval training (HIIT) is a time-efficient and e...

Rheumatoid arthritis (RA) impacts arterial and diastolic function. This study examined whether arterial properties can determine diastolic function in RA. In 173 RA patients, arterial function measures including carotid femoral pulse wave velocity (PWV), central systolic and pulse pressure, pulse pressure amplification, and the magnitude and timing...

We determined the role of high-grade inflammation on endothelial function and its association with biomarkers of endothelial dysfunction in collagen-induced arthritis. Sprague-Dawley rats were divided into a control (n = 12) or collagen-induced arthritis (CIA; n = 21) group. To induce arthritis, Bovine-type-II collagen emulsified in incomplete Freu...

The effect of hyperlipidemia on the cardiovascular system is uncertain in females. The aim of the present study was to determine whether administration of a lipogenic diet alters cardiovascular parameters in female rats. Fifty female Sprague-Dawley rats were assigned into 2 groups of rats receiving a standard or a high-fat, high-sucrose diet (HFHS)...

Background Aberrant hemostasis is implicated in the increased CVD risk experienced by patients with rheumatoid arthritis (RA) (1). Large circulating concentrations of plasminogen activator inhibitor-1 (PAI-1) predict cardiovascular event rates (2). PAI-1 levels are markedly smaller in American and African black populations than in those of European...

Purpose Multiday racing causes mild left ventricular (LV) dysfunction from day 1 that persists on successive days. We evaluated ingesting casein protein hydrolysate–carbohydrate (PRO) compared with carbohydrate-only (CHO) during a 3-day mountain bike race. Methods Eighteen male cyclists were randomly assigned to ingest 6.7% carbohydrate without (C...

Background Preventive pharmacotherapy for atherosclerotic cardiovascular disease (ACVD) is reportedly underused in patients with rheumatoid arthritis (RA). Whether this shortcoming is RA specific amongst patients with prevalent rheumatic and musculoskeletal diseases (RMD) is currently unknown. Objectives This study aimed to compare high ACVD risk...

Background Patients with rheumatic and musculoskeletal diseases (RMDs) from developed populations often experience increased atherosclerotic cardiovascular disease (ACVD) risk. In European countries, increasing proportions of inhabitants originate in developing countries and are therefore reportedly at an earlier epidemiological transition stage, w...

Background Patients with rheumatoid arthritis (RA) experience an increased risk of developing heart failure with a preserved ejection fraction. Although there is some evidence to support a role of chronic inflammation in the pathogenesis of impaired left ventricular (LV) function in RA,¹ the direct effects of inflammatory cytokines on the LV functi...

Background Patients with rheumatoid arthritis (RA) experience an increased frequency of heart failure with a preserved ejection fraction (HFpEF) (1). The treatment of HFpEF is currently suboptimal. Elucidation of the underlying pathophysiological mechanisms of HFpEF may provide potential targets for its management. Diastolic dysfunction often prece...

Background We recently reported that apelin concentrations are associated with reduced atherosclerosis and plaque vulnerability as well as improved aortic function in rheumatoid arthritis (RA)1,2. These relations were influenced by RA characteristics1,2. Besides protecting against atherosclerosis, apelin is also a vasoactive peptide that improves c...

Sodium (Na)-intake increases vascular reactivity. Whether low potassium (K)-intake affects vascular reactivity associated blood pressure (BP) changes is uncertain. This study aimed to determine whether Na-induced increases in BP and vascular reactivity are altered by low K-intake. Male Sprague-Dawley rats were assigned to three dietary groups for s...

Apelin can improve arterial function by enhancing the expression of endothelial nitric oxide synthase but this effect depends markedly on endothelial integrity. We hypothesized that inflammation influences the potential impact of apelin on arterial function in rheumatoid arthritis (RA). We assessed the associations of apelin concentrations with art...

Nesfatin is an anti-inflammatory molecule that reduces atherosclerotic cardiovascular risk. By contrast, visfatin has pro-inflammatory properties and is pro-atherogenic. We examined the potential impact of nesfatin and visfatin on atherosclerotic disease in 232 (113 black and 119 white) consecutive rheumatoid arthritis (RA) patients from 2 centers....

This study compared the estimated prevalence and potential determinants of left ventricular (LV) diastolic dysfunction upon applying different classification criteria in rheumatoid arthritis (RA). LV diastolic function was assessed echocardiographically by pulsed Doppler ( E/A ), tissue Doppler ( E/e′ , lateral and septal e′ ), and left atrial volu...

Objectives: Atherosclerotic cardiovascular disease risk is increased in rheumatoid arthritis (RA). Wave reflection occurs at arterial branching points, which are particularly prone to atherosclerosis. We explored the relationship of wave reflection with atherosclerosis in RA. Methods: One hundred and sixty three RA patients (110 white, 31 Asian,...

Background: Left ventricular (LV) diastolic dysfunction characterizes heart failure with a preserved ejection fraction. Although it is recognized that the renin-angiotensin-aldosterone-system (RAAS) decreases LV diastolic function, whether systemic angiotensinogen contributes to these effects is uncertain. Hence the aim was to determine the relati...

Objective: Arterial properties influence cardiovascular disease (CVD) risk. We identified potential determinants of arterial function in patients with rheumatoid arthritis (RA). Methods: Relationships of traditional cardiovascular risk factors and RA characteristics with arterial stiffness (pulse wave velocity), wave reflection (augmentation ind...

Background Heart failure contributes to the excess mortality experienced by patients with rheumatoid arthritis (RA) (1). Impaired diastolic function represents a pre-clinical cardiac alteration which is highly predictive of cardiac events and often progresses to heart failure. Diastolic dysfunction is the most common cause of heart failure in patie...

Background Nesfatin-1 comprises a peptide that is involved in appetite suppression, energy homeostasis and fluid regulation, and was recently documented to participate in a range of cardiometabolic pathways (1,2). There is currently a need for the identification of novel biomarkers in the elucidation of CVD risk and its stratification in persons wi...

Background In the non-rheumatoid arthritis (RA) population, arterial stiffness contributes to cardiovascular disease risk beyond brachial blood pressure and other established cardiovascular risk factors. The increased cardiovascular disease risk in RA is now well documented. In this regard, how RA impacts on arterial stiffness remains uncertain. O...

Omentin is an adipokine that reportedly protects against cardiometabolic risk. We investigated the relationships between omentin concentrations and subclinical cardiovascular disease in rheumatoid arthritis (RA). Omentin concentrations were measured in 213 (104 black; 109 white) RA patients. Relationships of omentin levels with those of endothelial...

Supplementary Table 1: Traditional risk factors and RA characteristics associated with diastolic function and left ventricular geometry. Supplemental Table 2: Non-significant associations of traditional risk factors and RA characteristics with markers of diastolic function and left ventricular geometry.

Background and aims: Apelin-APJ signaling reduces cardiovascular disease (CVD) risk. In rheumatoid arthritis (RA), the atherosclerosis burden and plaque vulnerability to rupture are increased. We explored relationships between apelin concentrations and subclinical CVD in RA. Methods: Apelin levels were measured in 235 (114 black, 121 white) RA p...

Objective: The impact of obesity or associated metabolic risk factors on left ventricular (LV) diastolic dysfunction (DD) may be modest in comparison to the effects of co-morbidities, such as increases in blood pressure (BP). We aimed to assess whether the impact of obesity (or associated insulin resistance) on LV diastolic function is enhanced by...

Objective: Decreases in brachial blood pressure (BP) may occur for several hours following a bout of exercise. Although aortic backward waves predict cardiovascular damage independent of brachial BP, whether decreases in aortic backward waves also occur post-exercise; the extent to which these changes exceed brachial BP changes; and the best metho...

No abstract available for this article.

Purpose Decreases in brachial blood pressure (BP) may occur for several hours following a bout of exercise. Although aortic backward waves predict cardiovascular damage independent of brachial BP, whether decreases in aortic backward waves also occur post-exercise in young-to-middle-aged hypertensives, the extent to which these changes exceed brach...

Background: Whether excess adiposity, associated metabolic abnormalities or alternative risk factors for left ventricular (LV) diastolic function are modified rather than mediated by geometric LV remodeling, is uncertain. Methods: Echocardiographic LV mass index (LVMI), relative wall thickness (RWT) and diastolic function (lateral and septal wal...

Objectives: Our objective was to examine associations of traditional and non-traditional cardiovascular risk factors with relative leukocyte telomere length and confounder adjusted relationships of relative telomere length with endothelial activation and carotid atherosclerosis in black and white African patients with rheumatoid arthritis (RA). M...

Cardiac function is often suppressed following prolonged strenuous exercise and this may occur partly because of an energy deficit. This study compared left ventricular (LV) function by 2-dimensional echocardiography and tissue Doppler imaging (TDI) before and after ∼2.5 h of cycling (2-h steady-state 60% peak aerobic power output plus 16 km time t...

Aims: The role of the adipokine, resistin in mediating increases in aortic stiffness is uncertain. We aimed to determine independent relations between circulating resistin concentrations and aortic pulse wave velocity (PWV) and wave reflection in a community-based sample with a high prevalence of untreated hypertension and obesity. Methods: Plas...

Although the adipokine resistin may play a role in heart failure, the mechanisms of this effect are uncertain. Relations with left ventricular mass (LVM) and function are uncertain. In 739 randomly selected participants from a community sample (43.6% obese), we assessed relations between circulating resistin concentrations and LVM index (LVMI), LVM...

To determine whether brachial blood pressure (BP)-independent relations between aortic pressure and cardiovascular damage are better explained by reflected (backward) (Pb) or forward (Pf) wave pressure effects. In 1174 participants from a community of African ancestry, we assessed central aortic pulse pressure (PPc), Pb, and Pf (radial applanation...

Obesity causes an increased blood pressure (BP). This effect may be diminished in communities of African descent. However, the impact of obesity on ambulatory or aortic BP, which are enhanced in groups of African ancestry, has not been assessed. We aimed to determine the extent to which obesity is related to variations in office, ambulatory and aor...

Objective: Aortic blood pressure (BP) predicts outcomes and is associated with end-organ measures independent of brachial BP. Whether this is accounted for by the impact of aortic forward or backward waves on variations in aortic-to-brachial BP amplification is uncertain. We aimed to determine whether brachial BP-independent relations between aorti...

The protein type most suitable for ingestion during endurance exercise is undefined. This study compared co-ingestion of either 15 g/h whey or casein hydrolysate with 63 g/h fructose: maltodextrin (0.8:1) on exogenous carbohydrate oxidation, exercise metabolism and performance. 2 h postprandial, 8 male cyclists ingested either: carbohydrate-only, c...

Certain commercial carbohydrate replacement products include slowly absorbed carbohydrates such as isomaltulose. Few studies have investigated the metabolic effects of ingesting isomaltulose during exercise and none have evaluated exercise performance and gastrointestinal comfort. Nine male cyclists participated postprandially during three trials o...

To determine whether kidney function independently relates to endothelial activation and ultrasound determined carotid atherosclerosis in black and white Africans with rheumatoid arthritis (RA). We calculated the Jelliffe, 5 Cockcroft-Gault equations, Salazar-Corcoran, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemio...

Aim: To determine whether blood pressure (BP) or an excess adiposity, both frequently observed comorbidities that independently relate to left ventricular diastolic dysfunction (LVDD), have a greater impact on LVDD at a community level. Methods: We assessed the relative independent impact of an excess adiposity versus BP on indices of LVDD as de...

Rheumatoid arthritis (RA) enhances the risk of cardiovascular disease to a similar extent as diabetes. Whereas atherogenesis remains poorly elucidated in RA, traditional and nontraditional risk factors associate similarly and additively with CVD in RA. Current recommendations on CVD risk stratification reportedly have important limitations. Further...

In the present study, we examined the potential impact of adiponectin on carotid ultrasound determined atherosclerosis in 210 (119 black and 91 white) RA patients in mixed regression models. Total adiponectin concentrations were smaller in patients with compared to those without the metabolic syndrome (MetS) defined waist criterion (median (range)...

Abstract Although exercise training is unable to improve obesity-associated decreases in left ventricular (LV) diastolic function, as assessed using chamber function measurements, the effects on LV diastolic myocardial function, as assessed using tissue Doppler imaging (TDI), are uncertain. In 32 overweight (n = 11) or obese (n = 21), sedentary or...

Whether changes in in-treatment 24-hour aortic blood pressure (BP) predict changes in left ventricular mass (LVM) in response to antihypertensive treatment better than 24-hour brachial BP is uncertain. We imputed 24-hour aortic pulse pressure (PPc) and the 24-hour aortic-to-brachial amplification ratio (PPb/PPc) from an equation that we derived in...

Whether 24-hour aortic as opposed to brachial blood pressure (BPb) adds to the ability of 24-hour BP to predict cardiovascular damage is uncertain. We imputed 24-hour central aortic pulse pressure (PPc) from an equation derived in 1179 participants. We showed that the relationship between the in-office PPc imputed using this equation and the radial...

Background: Although groups of African descent are particularly sensitive to blood pressure (BP) effects of salt intake, the role of obesity and insulin resistance in mediating this effect is uncertain. We determined whether obesity or insulin resistance is independently associated with urinary Na(+)/K(+)-BP relationships in a community sample of...

To determine whether exercise training-induced decreases in blood pressure (BP) can be explained by decreases in aortic systolic pressure augmentation in overweight or obese individuals. Thirty-five sedentary or recreationally active men and women (30-57 years) who were either overweight (40 %) or obese (60 %) completed 6 weeks of exercise training...

Aim: We determined whether left ventricular hypertrophy (LVH) which exceeds that predicted from workload [inappropriate LV mass (LVM(inappr))] is associated with reduced left ventricle (LV) systolic chamber function independent of and more closely than absolute or indexed left ventricular mass (LVM). Methods: In 626 randomly selected adult parti...

Aim: To assess the effects of 6-weeks of exercise-training and a period of detraining on aortic stiffness and central aortic blood pressure (BP) in young-to-middle-aged pre- and grade I hypertensives. Methods: Thirty-five sedentary or recreationally active men and women (30-57years) with untreated pre- or stage I hypertension completed 6-weeks of c...

The objective of the study was to determine and compare the magnitude and duration of post-exercise hypotension (PEH) during free-living conditions after an acute session of concurrent water and land exercise in individuals with prehypertension and hypertension. Twenty-one men and women (aged 52 ± 10 years) volunteered for the study. Participants c...