Etheresia Pretorius

Etheresia Pretorius
Stellenbosch University | SUN · Department of Physiological Sciences

PhD

About

275
Publications
141,111
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7,313
Citations
Introduction
Resia is a research authority in coagulation pathology and ultrastructure and her prominent and ground-breaking work has been internationally acknowledged by her peers. See http://www.resiapretorius.net
Additional affiliations
January 2004 - December 2012
University of Pretoria
Education
June 1995 - September 1998
University of Pretoria
Field of study
  • Biological Sciences

Publications

Publications (275)
Article
Factor XIII, a transglutaminase that plays a crucial role in clot formation, consists of subunits A and B. Single nucleotide polymorphisms in Factor XIII-A have been linked to thrombotic risk. In Type 2 Diabetes mellitus (T2DM), a hypercoagulable state is thought to contribute to the high mortality rate associated with thrombotic diseases. Due to t...
Article
The Serum Amyloid A (SAA) family of proteins is associated with various pathological conditions, including cancer. However, their role in cancer is incompletely understood. Here, we investigated the role of SAA1 in cell cycle regulation, apoptosis, survival signaling, metabolism, and metastasis in models of triple-negative breast cancer (TNBC), usi...
Article
The prevalence of type 2 diabetes mellitus (T2DM) has quadrupled within three decades since 1980, affecting 422 million adults in 2016. It remains one of the most common noncommunicable chronic diseases and the underlying risk factor for cardiovascular diseases worldwide. There are different underlying mechanisms that play a role in the development...
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Ischemic stroke is a debilitating multi-factorial cerebrovascular disorder, representing an area of tremendous unmet medical need. Combination treatment has been proposed as a promising therapeutic approach towards combating ischemic stroke. The present study employs in vitro oxygen glucose deprivation (OGD) model to evaluate the post-ischemic neur...
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Many studies indicate that there is a (mainly dormant) microbial component in the progressive development of Alzheimer-type dementias (ADs); and that in the case of Gram-negative organisms, a chief culprit might be the shedding of the highly inflammagenic lipopolysaccharide (LPS) from their cell walls. We have recently shown that a highly sensitive...
Article
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Objective: This review focusses on the erythrocytes (RBCs) and their structural changes during inflammation and impaired blood rheology. We discuss systemic inflammation and the effects of dysregulated inflammatory molecules. These pro-inflammatory molecules directly affect the haematological system, and particularly the RBCs, platelets and plasma...
Article
Background: Haemochromatosis is an iron-storage disease with different genetic mutations, characterized by an increased intestinal absorption of iron, resulting in a deposition of excessive amounts of iron in parenchymal cells. When the iron is released in the blood, it is left in an unliganded form, where it can participate in Haber-Weiss and Fen...
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Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, p...
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The thrombin-induced polymerisation of fibrinogen to form fibrin is well established as a late stage of blood clotting. It is known that Parkinson’s Disease (PD) is accompanied by dysregulation in blood clotting, but it is less widely known as a coagulopathy. In recent work, we showed that the presence of tiny amounts of bacterial lipopolysaccharid...
Article
Circulating cytokines, and particularly the interleukin (IL)-family are known to play an important role in inflammation. These molecules circulate in the blood and therefore have a direct effect on the plasma molecules and the formed elements like the erythrocytes and platelets. Aberrant coagulation (hypercoagulation or blood clots that form too ea...
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In recent work, we discovered that the presence of highly substoichiometric amounts (10-8molar ratio) of lipopolysaccharide (LPS) from Gram-negative bacteria caused fibrinogen clotting to lead to the formation of an amyloid form of fibrin. We here show that the broadly equivalent lipoteichoic acids (LTAs) from two species of Gram-positive bacteria...
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Tissue necrosis factor-α (TNF-α) and complement component 3 (C3) are two well-known pro-inflammatory molecules. When TNF-α is upregulated, it contributes to changes in coagulation and causes C3 induction. They both interact with receptors on platelets and erythrocytes (RBCs). Here, we look at the individual effects of C3 and TNF-α, by adding low le...
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Type 2 diabetes (T2D) has many cardiovascular complications, including a thrombotic propensity. Many such chronic, inflammatory diseases are accompanied (and may be exacerbated, and possibly even largely caused) by amyloid fibril formation. Recognising that there are few strong genetic associations underpinning T2D, but that amyloidogenesis of amyl...
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Background We have previously shown that many chronic, inflammatory diseases are accompanied, and possibly partly caused or exacerbated, by various coagulopathies, manifested as anomalous clots in the form of ‘dense matted deposits’. More recently, we have shown that these clots can be amyloid in nature, and that the plasma of healthy controls can...
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Aspartame is a synthetic dipeptide artificial sweetener, frequently used in foods, medications, and beverages, notably carbonated and powdered soft drinks. Since 1981, when aspartame was first approved by the US Food and Drug Administration, researchers have debated both its recommended safe dosage (40 mg/kg/d) and its general safety to organ syste...
Article
The inflammatory burden of the complex Rheumatoid Arthritis (RA) disease affects several organ-systems, including rheological properties of blood and its formed elements. Red blood cells (RBCs) are constantly exposed to circulating dysregulated inflammatory molecules that are co-transported within the vasculature; and their membranes may be particu...
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A well-established development of increasing disease severity leads from sepsis through systemic inflammatory response syndrome, septic shock, multiple organ dysfunction syndrome, and cellular and organismal death. Less commonly discussed are the equally well-established coagulopathies that accompany this. We argue that a lipopolysaccharide-initiat...
Chapter
Type 2 diabetes (T2D) has attained a pandemic status with more than half a billion cases expected by 2030; and many having cardiovascular complications, with main hallmark of these events, the presence of systemic (chronic) inflammation. Systemic inflammation is in turn characterized by a changed haematological system, including a pathologic coagul...
Article
As erythrocyte and estrogens interact so closely and erythrocytes can indicate the healthiness of an individual, it is essential to investigate the effects of natural estrogens as well as synthetic estrogens on these cells. Whole blood samples were used for thromboelastography (TEG), light microscopy (LM), and scanning electron microscopy (SEM) inv...
Article
Combined oral contraceptive (COC) use is a risk factor for venous thrombosis (VT) and related to the specific type of progestin used. VT is accompanied by inflammation and pathophysiological clot formation, that includes aberrant erythrocytes and fibrin(ogen) interactions. In this paper, we aim to determine the influence of progesterone and differe...
Article
Background: Clotting parameters are informative of overall haematological healthiness of an individual. Particularly, clotting parameters can be used as a measure of the degree of pathology of the coagulation system. Thromboelastography (TEG) is a well-known technique that is an important point-of-care method, as well as research method. Scanning...
Chapter
The progression of Alzheimer's disease (AD) is accompanied by a great many observable changes, both molecular and physiological. These include oxidative stress, neuroinflammation, and (more proximal to cognitive decline) the death of neuronal and other cells. A systems biology approach seeks to organize these observed variables into pathways that d...
Article
Introduction: Type 2 diabetes mellitus is a pandemic associated with disturbance in haemostasis that could contribute to the development of diabetic vascular disease and accelerated atherosclerosis. In this population, hypercoagulation is prevalent, as well as pathological changes to erythrocytes. This is mainly due to upregulated circulating infl...
Article
Estrone (E1 ) and Estriol (E3 ) are endogenous female hormones, present in increased concentrations during female specific physiological processes (menopause and pregnancy respectively) that are associated with increased venous thrombotic risk. These hormones are also used as hormone therapies that are also associated with increased thromboembolism...
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Type II diabetes (T2D) is a pandemic characterized by pathological circulating inflammatory markers, high-glucose levels and oxidative stress. The hematological system is especially vulnerable to these aberrant circulating molecules, and erythrocytes (RBCs) show aberrant rheology properties, owing to the direct contact with these molecules. Patholo...
Article
The progression of Alzheimer's disease (AD) is accompanied by a great many observable changes, both molecular and physiological. These include oxidative stress, neuroinflammation, and (more proximal to cognitive decline) the death of neuronal and other cells. A systems biology approach seeks to organize these observed variables into pathways that d...
Article
We review the evidence that infectious agents, including those that become dormant within the host, have a major role to play in much of the etiology of rheumatoid arthritis and the inflammation that is its hallmark. This occurs in particular because they can produce cross-reactive (auto-)antigens, as well as potent inflammagens such as lipopolysac...
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A significant burden of illness is caused globally by snakebites particularly by the puff adder, Bitis arietans. Presently there is no reliable and rapid method to confirm envenomation on blood chemistry; although coagulation parameters like prothrombin time, partial thromboplastin time, international normalized ratio and also serum electrolytes ar...
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The latest statistics from the 2016 heart disease and stroke statistics update shows that cardiovascular disease is the leading global cause of death, currently accounting for more than 17.3 million deaths per year. Type II diabetes is also on the rise with out-of-control numbers. To address these pandemics, we need to treat patients using an indiv...
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Erythrocytes (RBCs) are extremely sensitive cells, and although they do not have nuclei and mitochondria, are important health indicators. This is particularly true because, during inflammation, whether it is systemic or chronic, the haematological system is constantly exposed to circulating inflammatory mediators. RBCs have a highly specialized an...
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Complex interactions exist between cytokines, and the interleukin family plays a fundamental role in inflammation. Particularly circulating IL-1β, IL-6 and IL-8 are unregulated in systemic and chronic inflammatory conditions. Hypercoagulability is an important hallmark of inflammation, and these cytokines are critically involved in abnormal clot fo...
Article
Full-text available
It is well known that a variety of inflammatory diseases are accompanied by hypercoagulability, and a number of more-or-less longer-term signalling pathways have been shown to be involved. In recent work, we have suggested a direct and primary role for bacterial lipopolysaccharide (LPS) in this hypercoagulability, but it seems never to have been te...
Article
Full-text available
Complex interactions exist between cytokines, and the interleukin family plays a fundamental role in inflammation. Particularly circulating IL-1β, IL-6 and IL-8 are unregulated in systemic and chronic inflammatory conditions. Hypercoagulability is an important hallmark of inflammation, and these cytokines are critically involved in abnormal clot fo...
Article
Full-text available
The chief and largely terminal element of normal blood clotting is considered to involve the polymerisation of the mainly α-helical fibrinogen to fibrin, with a binding mechanism involving ‘knobs and holes’ but with otherwise little change in protein secondary structure. We recognise, however, that extremely unusual mutations or mechanical stressin...
Article
Combined oral contraceptives (COCs), colloquially referred to as “the pill,” have been regarded as a medical breakthrough, as they have improved the lives of countless women, from simplifying family planning to the treatment of acne, endometriosis, polycystic ovarian syndrome, and dysmenorrhea. Unfortunately, COC usage has been associated with an i...
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Objectives Type 2 diabetes patients (T2D) have a considerably higher cardiovascularrisk, which is closely associated with systemic inflammation, and an accompanying pathologic coagulation system. Due to the complexity of the diabetic profile, we suggest that we need to look at each patient individually and particularly at his or her clotting profil...
Article
Full-text available
The progression of Alzheimer's disease (AD) is accompanied by a great many observable changes, both molecular and physiological. These include oxidative stress, neuroinflammation, and (more proximal to cognitive decline) the death of neuronal and other cells. A systems biology approach seeks to organize these observed variables into pathways that d...
Article
Full-text available
The function of platelets have extended way beyond the horizon of haemostasis and thrombosis, and are recognised as active participants in vascular inflammation, as well as in prothrombotic complications of cardiovascular diseases. We describe and compare platelet function in type II diabetes (with and without cardiovascular manifestation) and heal...
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In summary, we propose that infectious agents, including HSV1, Chlamydia pneumonia, and spirochetes, reach the CNS and remain there in latent form. These agents can undergo reactivation in the brain during aging, as the immune system declines, and during different types of stress (which similarly reactivate HSV1 in the periphery). The consequent ne...
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Central to the pathogenesis of ischaemic stroke are the normally protective processes of platelet adhesion and activation. Experimental evidence has shown that the ligand-receptor interactions in ischaemic stroke represent a thrombo-inflammatory cascade, which presents research opportunities into new treatment. However, as anti-platelet drugs have...
Article
Transient ischemic attack (TIA) is an important predictor of future ischemic events, including stroke. Due to the typically brief period of neurologic dysfunction, patients often overlook the importance of reporting a TIA. We have recently shown that platelet activation plays an important role in TIA pathology. In a similar vein, smoking is associa...
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Adult rheumatoid arthritis (RA) is an autoimmune disorder affecting joints and frequently characterised by initial local and later systemic inflammation. Researchers have, for many years, traced its cause to diverse genetic, environmental and especially immunological responses that work against the body's own cells and tissues. Investigation into s...
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We have noted in previous work, in a variety of inflammatory diseases, where iron dysregulation occurs, a strong tendency for erythrocytes to lose their normal discoid shape and to adopt a skewed morphology (as judged by their axial ratios in the light microscope and by their ultrastructure in the SEM). Similarly, the polymerization of fibrinogen,...
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Background Platelets are known contributors to the vascularization, metastasis and growth of tumors. Upon their interaction with cancer cells they are activated resulting in degranulation and release of constituents. Since the apoptotic- and autophagic effects of 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) has been shown to occur in...
Article
Stroke is one of the most debilitating thrombotic diseases, and world-wide it is estimated that by, 2030, 23 million people will be affected. Except for the impact on the individual families, the world economy is also affected adversely. Although the medical treatment and knowledge of stroke are both increasing and well-researched, we still do not...
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Alzheimer-type dementia (AD) is a neurodegenerative disorder and the most common form of dementia. Patients typically present with neuro- and systemic inflammation and iron dysregulation, associated with oxidative damage that reflects in hypercoagulability. Hypercoagulability is closely associated with increased fibrin(ogen) and in AD patients fibr...
Article
Angiogenesis is a closely controlled biological process that takes place during fetal development of blood vessels and wound healing, and includes the development of new blood vessels from preexisting blood vessels. Tumor angiogenesis is a means by which tumors obtain oxygen, nutrition and promote tumor growth. Angiogenesis-regulating proteins are...
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We have recently highlighted (and added to) the considerable evidence that blood can contain dormant bacteria. By definition, such bacteria may be resuscitated (and thus proliferate). This may occur under conditions that lead to or exacerbate chronic, inflammatory diseases that are normally considered to lack a microbial component. Bacterial cell w...
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For bacteria, replication mainly involves growth by binary fission. However, in a very great many natural environments there are examples of phenotypically dormant, non-growing cells that do not replicate immediately and that are phenotypically 'nonculturable' on media that normally admit their growth. They thereby evade detection by conventional c...
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Accelerated atherosclerosis is the main underlying factor contributing to the high risk of atherothrombotic events in patients with diabetes mellitus and atherothrombotic complications are the main cause of mortality. Like with many bodily systems, pathology is observed when the normal processes are exaggerated or uncontrolled. This applies to the...
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Strokes are commonly preceded by transient ischemic attacks (TIAs). TIA is often associated with metabolic syndrome (causing chronic inflammation), resulting in a proinflammatory- and procoagulant-environment. The aim of this study was to determine whether platelet- and fibrin network-morphology or coagulation profiles of individuals that suffered...
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Full-text available
For bacteria, replication mainly involves growth by binary fission. However, in a very great many natural environments there are examples of phenotypically dormant, non-growing cells that do not replicate immediately and that are phenotypically ‘nonculturable’ on media that normally admit their growth. They thereby evade detection by conventional c...
Article
Full-text available
Cytokines, lymphocytes, platelets and several biomolecules have long been implicated in the pathology of rheumatoid arthritis (RA), and the influences of antibody production and tagging, and cytokine, chemokine and enzyme production at specific rheumatoid joints were thought to be exclusive to the advancement of disease parameters. Another role pla...
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Blood in healthy organisms is seen as a 'sterile' environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. 'Non-culturability', reflected by discrepancie...
Article
The FYB gene encodes the adhesion and degranulation-promoting adapter protein (ADAP), a hematopoietic-specific protein involved in platelet activation, cell motility and proliferation, and integrin-mediated cell adhesion. No ADAP-related diseases have been described in humans, but ADAP-deficient mice have mild thrombocytopenia and increased re-blee...