Mattias Carlström

Mattias Carlström
Karolinska Institutet | KI · Department of Physiology and Pharmacology

PhD, PharmD, Professor of Cardiorenal Physiology

About

202
Publications
31,242
Reads
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4,758
Citations
Citations since 2017
104 Research Items
3465 Citations
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Introduction
Emerging evidence suggests that renal oxidative stress and nitric oxide (NO) deficiency is linked to cardiovascular disease and diabetic complications. Mechanisms are not clear, but exaggerated NADPH oxidase-derived superoxide production and NO deficiency may impair renal autoregulation. Using a translational design, our projects aim to characterize the mechanisms for superoxide and NO formation, interaction and influence on renal, cardiovascular and metabolic functions in health and disease.
Additional affiliations
January 2016 - present
Karolinska Institutet
Position
  • Professor (Associate)
January 2012 - January 2016
Karolinska Institutet
Position
  • Professor (Assistant)
January 2012 - present
Karolinska Institutet
Position
  • Research Assistant
Description
  • Renal and Cardiovascular Function
Education
August 2003 - April 2008
Uppsala University
Field of study
  • Physiology (Faculty of Medicine)
August 1998 - June 2003
Uppsala University
Field of study
  • Pharmaceutical Science

Publications

Publications (202)
Article
The metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for cardiovascular disease and type 2 diabetes. A proposed central event in metabolic syndrome is a decrease in the amount of bioavailable nitric oxide (NO) from endothelial NO synthase (eNOS). Recently, an alternative pathway for NO formation in mamma...
Article
Renal oxidative stress and nitric oxide (NO) deficiency are key events in hypertension. Stimulation of a nitrate-nitrite-NO pathway with dietary nitrate reduces blood pressure, but the mechanisms or target organ are not clear. We investigated the hypothesis that inorganic nitrate and nitrite attenuate reactivity of renal microcirculation and blood...
Article
Oxidative stress contributes to the pathogenesis of many disorders, including diabetes and cardiovascular disease. Immune cells are major sources of superoxide (O2(•-)) as part of the innate host defense system, but exaggerated and sustained O2(•-) generation may lead to progressive inflammation and organ injuries. Previous studies have proven orga...
Article
Full-text available
Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80-180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor to...
Article
Full-text available
The prevalence of cardiovascular and metabolic disease coupled with kidney dysfunction is increasing worldwide. This triad of disorders is associated with considerable morbidity and mortality as well as a substantial economic burden. Further understanding of the underlying pathophysiological mechanisms is important to develop novel preventive or th...
Article
Background & aims Nitric oxide bioactivity (NO) from endothelial NO synthase (eNOS) importantly contributes to the maintenance of vascular homeostasis, and reduced eNOS activity has been associated with cardiovascular disease. Emerging evidence suggest interaction(s) between red blood cells (RBCs) and the endothelium in vascular control; however, t...
Chapter
Type 2 diabetes (T2D) is a complex metabolic disorder characterized by impaired glucose metabolism and pancreatic β-cell dysfunction. No effective treatments are available for T2D, although there have been many developments in the therapeutic arena. Nitric oxide (NO) is an endocrine agent with multiple and important biological roles in most mammali...
Chapter
Type 2 diabetes (T2D) is a complex metabolic disorder characterized by impaired glucose metabolism and pancreatic β-cell dysfunction. No effective treatments are available for T2D, although there have been many developments in the therapeutic arena. Nitric oxide (NO) is an endocrine agent with multiple and important biological roles in most mammali...
Chapter
Type 2 diabetes (T2D) is a complex metabolic disorder characterized by impaired glucose metabolism and pancreatic β-cell dysfunction. No effective treatments are available for T2D, although there have been many developments in the therapeutic arena. Nitric oxide (NO) is an endocrine agent with multiple and important biological roles in most mammali...
Article
Full-text available
Aims: Cardiac contractile dysfunction is prevalent in rheumatoid arthritis (RA), with increased risk for heart failure. A hallmark of RA is increased levels of peptidyl arginine deaminases (PAD) that convert arginine to citrulline leading to ubiquitous citrullination, including in the heart. We aimed to investigate whether PAD-dependent citrullina...
Article
Full-text available
Arginase 1 (Arg1) is a ubiquitous enzyme belonging to the urea cycle that catalyzes the conversion of l-arginine into l-ornithine and urea. In endothelial cells (ECs), Arg1 was proposed to limit the availability of l-arginine for the endothelial nitric oxide synthase (eNOS) and thereby reduce nitric oxide (NO) production, thus promoting endothelial...
Article
Full-text available
Nitric oxide (NO) contributes to maintaining normal cardiovascular and renal function. NO is generally formed enzymatically by NO synthase in the vascular endothelium. NO bioactivity can also be attributed to dietary intake of inorganic nitrate, which is abundant in our diet, especially in green leafy vegetables and beets. Ingested nitrate is reduc...
Article
Full-text available
Adenine nucleotide translocases (ANTs) and uncoupling proteins (UCPs) are known to facilitate proton leak across the inner mitochondrial membrane. However, it remains to be unravelled whether UCP2/3 contribute to significant amount of proton leak in vivo . Reports are indicative of UCP2 dependent proton-coupled efflux of C4 metabolites from the mit...
Article
Decreased heart levels of nitric oxide (NO) and hydrogen sulfide (H2S) in type 2 diabetes (T2D) are associated with a higher risk of mortality following ischemia-reperfusion (IR) injury. This study aimed to determine the effects of co-administration of sodium nitrite and sodium hydrosulfide (NaSH) on IR injury in the isolated heart from rats with T...
Article
Full-text available
Background Renal fibrosis, associated with oxidative stress and nitric oxide (NO) deficiency, contributes to the development of chronic kidney disease and renal failure. As major energy source in maintaining renal physiological functions, tubular epithelial cells with decreased fatty acid oxidation play a key role in renal fibrosis development. Ino...
Article
Full-text available
Rationale Dietary nitrate and nitrite have a notoriously bad reputation because of their proposed association with disease, in particular cancer. However, more recent lines of research have challenged this dogma suggesting that intake of these anions also possess beneficial effects after in vivo conversion to the vital signaling molecule nitric oxi...
Article
Organic nitrates are widely used to restore endogenous nitric oxide (NO) levels reduced by endothelial nitric oxide synthase dysfunction. However, these drugs are associated with undesirable side effects, including tolerance. This study aims to investigate the cardiovascular effects of the new organic nitrate 1,3-diisobutoxypropan-2-yl nitrate (NDI...
Article
Oral microbiota dysbiosis, concomitant with decreased abundance of nitrate (NO3⁻)-reducing bacteria, oral net nitrite (NO2⁻) production, and reduced nitric oxide (·NO) bioactivity, is associated with the development of cardiometabolic disorders. Therefore, restoring the oral microbiome to a health-associated state is suggested as a therapeutic appr...
Article
Full-text available
The study evaluated the effect of the supernatant of placental explants from preeclamptic (PE) and normotensive (NT) pregnant women after tissue treatment with or without vitamin D (VD) on oxidative stress and nitric oxide (NO) bioavailability in human umbilical vein endothelial cells (HUVEC). Placental explants were prepared from eight NT and eigh...
Preprint
Full-text available
Vasodilation is a cornerstone of inflammation physiology. By regulating vasodilation and tissue entry of T cells, CD4+ T lymphocytes expressing choline acetyltransferase (ChAT), a key enzyme for biosynthesis of the vasorelaxant acetylcholine (ACh), critically link immunity with vascular biology in mice. However, the characterization of primary huma...
Article
Full-text available
Rationale: Pre-eclampsia is a multisystem disorder associated with systemic vascular dysfunction and decreased nitric oxide (NO) bioactivity. Arginase competes with NO synthase (NOS) for L-arginine, and its upregulation may reduce NOS-derived NO formation or induce production of reactive oxygen species (ROS) via uncoupling of NOS, resulting in end...
Article
Full-text available
Background and aims Preeclampsia (PE) is a gestational hypertensive disease responsible for high maternal and fetal morbidity and mortality. The increase in blood pressure is associated with a decrease in the bioavailability of nitric oxide (NO). Arginase interferes with NO production consuming L-arginine, a substrate required by endothelial NO syn...
Article
Full-text available
Objective: To investigate whether the supernatant from monocytes of preeclamptic and normotensive pregnant women, cultured in vitro with silibinin, can modulate oxidative stress in HUVEC. Methods: Concentrations of IL-1β, IL-10, and TNF-α in monocyte culture supernatants were determined by ELISA. HUVEC and their supernatant cultures were employed f...
Article
Full-text available
Background: Renal ischemia-reperfusion (IR) injury is a common cause of acute kidney injury (AKI), which is associated with oxidative stress and reduced nitric oxide (NO) bioactivity and increased risk of developing chronic kidney disease (CKD) and cardiovascular disease (CVD). New strategies that restore redox balance may have therapeutic implica...
Article
Full-text available
Aim The inorganic anions nitrate and nitrite are oxidation products of nitric oxide (NO) that have often been used as an index of NO generation. More than just being surrogate markers of NO, nitrate/nitrite can recycle to bioactive NO again. Nitrate is predominantly eliminated via the kidneys, however, there is less knowledge regarding the tubular...
Article
Heart failure (HF) results in a myriad of central and peripheral abnormalities that impair the ability to sustain skeletal muscle contractions and, therefore, limit tolerance to exercise. Central to these abnormalities is the lowered maximal oxygen uptake, which is brought about by reduced cardiac output and exacerbated by O 2 delivery-utilization...
Article
Full-text available
Aim: Studies in the past 15 years have highlighted the role of the gut microbiota in modulation of host metabolism. The observation that germ-free (GF) mice are leaner than conventionally raised (CONV) mice and their apparent resistance to diet-induced obesity (DIO), sparked the interest in dissecting the possible causative role of the gut microbio...
Article
Introduction Cardiovascular diseases are coupled to decreased nitric oxide (NO) bioavailability, and there is a constant search for novel and better NO-donors. Here we synthesized and characterized the cardiovascular effects of the new organic nitrate 2-nitrate-1,3-dioctanoxypropan (NDOP). Methods A combination of in vitro and in vivo experiments...
Article
Objective A deficiency in hydrogen sulfide (H2S) and nitric oxide (NO) contributes to the development of type 2 diabetes (T2D). An inhibitory effect on liver gluconeogenesis has been reported in rats with T2D with co-administration of sodium nitrite and sodium hydrosulfide (NaSH); the underlying mechanisms have however not yet been elucidated. The...
Article
Full-text available
It is becoming increasingly clear that commensal bacteria inhabiting our body surfaces interact closely with the host to modulate a vast number of physiological functions. Metabolism of dietary components by gut microbiota can result in formation of a variety of reactive compounds associated with both favorable and unfavorable health effects. N-nit...
Article
Full-text available
Growth plate and articular cartilage constitute a single anatomical entity early in development but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears in animals conquering the land - amniotes. Analysis of the ossification p...
Article
Full-text available
Growth plate and articular cartilage constitute a single anatomical entity early in development but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears in animals conquering the land - amniotes. Analysis of the ossification p...
Article
Full-text available
Growth plate and articular cartilage constitute a single anatomical entity early in development, but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears in animals conquering the land - amniotes. Analysis of ossification patt...
Article
Aim We aimed to compare the pharmacokinetics of nitrate (NO3) in patients with type 2 diabetes mellitus (T2DM) and healthy adults. Potential effects of salivary nitrate reductase (NR) activity on cardiometabolic responses to an acute dose of NO3 was also assessed. Methods Nine healthy adults and nine T2DM patients were recruited to consume a NO3-r...
Article
Objective Subjects with type 2 diabetes (T2D) have lower circulating hydrogen sulfide (H2S) levels following myocardial ischemia and a higher risk of mortality. The aim of this study was to determine the dose-dependent favorable effects of sodium hydrosulfide (NaSH) on myocardial ischemia-reperfusion (IR) injury in rats with T2D. Methods T2D was i...
Article
Mitochondria play fundamental role in maintaining cellular metabolic homeostasis, and metabolic disorders including type 2 diabetes (T2D) have been associated with mitochondrial dysfunction. Pathophysiological mechanisms are coupled to increased production of reactive oxygen species and oxidative stress, together with reduced bioactivity/signaling...
Article
Full-text available
Background: A diet rich in fruits and vegetables is associated with lowering of blood pressure (BP), but the nutrient(s) responsible for these effects remain unclear. Research suggests that inorganic nitrate present in leafy green vegetables is converted into NO in vivo to improve cardiovascular function. Objective: In this study, we evaluated t...
Article
Full-text available
Decreased circulating levels of hydrogen sulfide (H2S) are associated with higher mortality following myocardial ischemia. This study aimed at determining the long-term dose-dependent effects of sodium hydrosulfide (NaSH) administration on myocardial ischemia-reperfusion (IR) injury. Male rats were divided into control and NaSH groups that were tre...
Article
Full-text available
Hyperuricemia is characterized by abnormally high level of circulating uric acid in the blood and is associated with increased risk of kidney injury. The pathophysiological mechanisms leading to hyperuricemic nephropathy (HN) involve oxidative stress, endothelial dysfunction, inflammation, and fibrosis. Mangiferin is a bioactive C-glucoside xanthon...
Article
Full-text available
Background/purpose: Unhealthy dietary habits contribute to the increasing incidence of metabolic syndrome and type 2 diabetes (T2D), which is accompanied by oxidative stress, compromised nitric oxide (NO) bioavailability and increased cardiovascular risk. Apart from lifestyle changes, biguanides such as metformin are the first-line pharmacological...
Article
Background & purpose It is well established that end-stage renal disease (ESRD) is associated with increased cardiovascular morbidity and mortality both in the adult and pediatric population. Although the underlying molecular mechanisms are poorly understood, compromised nitric oxide (NO) bioactivity has been suggested as a contributing factor. Wit...
Article
Nitric oxide (NO), a highly‐reactive gasotransmitter, is critical for a number of cellular processes and has multiple biological functions. Due to its limited lifetime and diffusion distance, NO has been mainly believed to act in autocrine/paracrine fashion. The increasingly recognized effects of pharmacologically delivered and endogenous NO at a d...
Article
Aging is associated with decreased nitric oxide (NO) bioavailability and signalling. Boosting of a dietary nitrate-nitrite-NO pathway e.g. by ingestion of leafy green vegetables, improves cardiometabolic function, mitochon-drial efficiency and reduces oxidative stress in humans and rodents, making dietary nitrate and nitrite an appealing interventi...
Article
Full-text available
Background/objectives: Maternal obesity together with androgen excess in mice negatively affects placental function and maternal and fetal liver function as demonstrated by increased triglyceride content with dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage. To identify changes in molecu...
Article
Full-text available
Emerging evidence indicates that dietary nitrate can reverse several features of the metabolic syndrome, but the underlying molecular mechanisms still remain elusive. The aim of the present study was to explore mechanisms involved in the effects of dietary nitrate on the metabolic dysfunctions induced by high-fat diet (HFD) in mice. Four weeks old...
Article
Nitric oxide (NO) is a key signalling molecule in the regulation of cardiometabolic function and impaired bioactivity is considered to play an important role in the onset and progression of cardiovascular and metabolic disease. Research has revealed an alternative NO-generating pathway, independent of NO synthase (NOS), in which the inorganic anion...
Article
Aims: Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is suggested to increase the risk for cardiovascular disease. How PCOS may lead to adverse cardiac outcomes is unclear and here we hypothesized that prenatal exposure to dihydrotestosterone (DHT) and/or maternal obesity in mice induce adverse metabolic and cardiac programming i...
Article
Aims: Vascular calcification, a marker of increased cardiovascular risk, is an active process orchestrated by smooth muscle cells. Observational studies indicate that omega-3 fatty acids protect against vascular calcification, but the mechanisms are unknown. The G-protein coupled receptor ChemR23 transduces the resolution of inflammation induced b...
Article
The nitrate‐nitrite‐nitric oxide (NO) pathway represents an alternative source of NO generation, which is independent of NO synthase and potentiated by hypoxia. Augmentation of this pathway by dietary nitrate has proven favourable effects in several cardiovascular disease models. However, less is known regarding its potential value in pulmonary art...
Article
Objective: Decreased nitric oxide (NO) bioavailability and hydrogen sulfide (H2S) deficiency have been linked with the pathophysiology of type 2 diabetes (T2D). Restoration of NO levels by nitrite have been associated with favorable metabolic effects in T2D. Moreover, H2S can potentiate the effects of NO in the cardiovascular system. The aim of th...
Article
Background: Kidney transplantation is associated with increased cardiovascular risk. Endothelial dysfunction and vascular inflammation contribute to negative outcome. In experimental models, mineralocorticoid receptor antagonists (MRA) improved endothelial function and reduced inflammation. The current study tested the hypothesis that the MRA spir...
Article
BACKGROUND: Nitrosation of a conserved cysteine residue at position 93 in the hemoglobin β chain (β93C) to form S-nitroso (SNO) hemoglobin (Hb) is claimed to be essential for export of nitric oxide (NO) bioactivity by the red blood cell (RBC) to mediate hypoxic vasodilation and cardioprotection. METHODS: To test this hypothesis, we used RBCs from...
Article
Background Early differentiation between perforated and nonperforated acute appendicitis (AA) in children is of major benefit for the selection of proper treatment. Based on pilot study data, we hypothesized that plasma sodium concentration at hospital admission is a diagnostic marker for perforation in children with AA. Materials and Methods This...
Article
Polycystic ovary syndrome (PCOS) is suggested to increase the risk for cardiovascular disease and type 2 diabetes. We hypothesized here that prenatal exposure to dihydrotestosterone (DHT) and/or maternal obesity lead to adverse metabolic and cardiac programming in the female offspring. The maternal obese PCOS phenotype was induced in mice by prenat...
Preprint
Full-text available
The growth of long bones occurs in narrow discs of cartilage, called growth plates that provide a continuous supply of chondrocytes subsequently replaced by newly formed bone tissue. These growth plates are sandwiched between the bone shaft and a more distal bone structure called the secondary ossification center (SOC). We have recently shown that...
Article
Emerging data suggest that impaired nitric oxide (NO) homeostasis has a key role in development of cardiometabolic disorders. The association between circulating levels of NO metabolites, ie nitrate and nitrite (NOx), and risk of chronic diseases has not yet been fully clarified. This work aims to address epidemiologic aspects of NO metabolism and...
Article
Several experimental and clinical studies have shown that dietary nitrate supplementation can increase nitric oxide bioavailability. In the oral cavity, commensal bacteria reduce nitrate to nitrite, which is subsequently absorbed into the circulation where reduction to nitric oxide by enzymatic systems occur. Although it is well-known that boosting...
Article
Full-text available
Significance Liver steatosis, or fatty liver, is the most common liver disease in the world, affecting up to 25% of all Americans. There is currently no approved drug available for this condition, which may progress to serious disease, including steatohepatitis, fibrosis, and cirrhosis. Here, we show in rodent and human models of metabolic syndrome...
Article
Full-text available
Background Resolution of inflammation is an active and dynamic process after surgery. Maresin 1 (MaR1) is one of a growing number of specialised pro-resolving lipids biosynthesised by macrophages that regulates acute inflammation. We investigated the effects of MaR1 on postoperative neuroinflammation, macrophage activity, and cognitive function in...
Presentation
Research during the last two decades have revealed that supplementation with inorganic nitrate (NO3-), which is highly abundant in leafy green vegetables, can increase endogenous formation of nitric oxide (NO) via the so called NO3-NO2-NO pathway. Chronic treatment with NO3 or acute treatment with nitrite (NO2-) has been associated with favorable e...
Data
Supplemental Figures and Source Data for Western Blots to Scientific Reports article by Tassi and Garman et al., DOI: 10.1038/s41598-018-34238-5
Data
Supplemental Methods to Scientific Reports article by Tassi and Garman et al., DOI: 10.1038/s41598-018-34238-5