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At least 883 records · Page 49Linked to original sources
PubMed2000

Sublytic complement attack increases intracellular sodium in rat skeletal muscle.

BACKGROUND: Although excessive complement activation and deranged sodium homeostasis in skeletal muscle are characteristic in sepsis, their relationship has not been examined. This study was designed to determine if sublytic complement activation can directly mediate changes in myocellular sodium content. MATERIALS AND METHODS: Fast-twitch extensor digitorum longus muscles were freshly isolated from infant rats. Unsensitized muscles were incubated at 30 degrees C for 60 min in the media containing 10% human or rat serum under conditions of no complement activation, activation by zymosan, inactivation by heat, C7 or C9 deficiency, selective inhibition of complement pathway, and inhibition of Na(+)-K(+) ATPase by ouabain. Intracellular sodium ([Na(+)](i)) and potassium ([K(+)](i)) contents of the muscles, myocellular ATP, and LDH release from the muscles were then determined. RESULTS: Normal human serum significantly increased [Na(+)](i) and the [Na(+)](i)/[K(+)](i) ratio in the muscles as well as zymosan-activated serum. Heat inactivation, C7 deficiency, and inhibition of the alternative pathway completely abolished the cationic changes. Average LDH release was identical in all groups and less than 6%. Complement activation did not impair ouabain-sensitive Na(+)-K(+) ATPase activity in the muscles or alter myocellular ATP. Thus, the observed alterations are not likely due to dysfunction of Na(+)-K(+) pump or depletion of myocellular energy. Instead, alterations in [Na(+)](i) were dependent upon the amount of C9 added to C9-deficient serum, which suggests that the alterations are likely dependent on transmembrane pores created by membrane attack complexes (MAC). CONCLUSIONS: Sublytic amounts of MAC formed as a result of complement activation can directly alter [Na(+)](i) in ex vivo skeletal muscle.

Adenosine Triphosphate↗
PubMed1995

Biochemical studies of isolated mitochondria from normal and diseased tissues.

Isolated mitochondria have served as useful tools for identifying the site(s) of impairment associated with respiratory chain-linked oxidative phosphorylation at the molecular level. Over the last three decades, a number of diseases associated with mitochondrial dysfunction have been identified. The literature is large and diverse. This paper presents a brief survey of the current state of knowledge concerning biochemical studies of mitochondrial diseases associated with skeletal muscle, such as mitochondrial myopathies and, with brain injury such as that induced by ischemia/reperfusion. Various mitochondrial preparations and assay conditions are evaluated. The importance of fresh tissue for the isolation of tightly coupled mitochondria and the selection of suitable assay conditions for characterization have been demonstrated. Appropriate methodologies for isolation and characterization of tightly coupled mitochondria from both skeletal muscle and brain are presented.

Animals↗
PubMed2002

Incorporation and integration of implanted myogenic and stem cells into native myocardial fibers: anatomic basis for functional improvements.

BACKGROUND: Myoblasts and stem cells implanted into myocardium can differentiate into myocytes and may functionally improve impaired ventricles. For implanted cells to actually contribute to the synchronous contractions of the heart, however, they must be anatomically integrated with the existing native myocardial fibers. METHODS: Isogenic Lewis rats were used as donors and recipients to simulate clinical autotransplantation. Either skeletal myoblasts or marrow stromal stem cells were isolated from donors, culture expanded, and labeled with 4',6-diamidino-2-phenylindole (4',6-diamidino-2-phenylindole). Labeled cells were then injected into the myocardium of recipients. At intervals specimens were obtained, sectioned, and stained with hematoxylin and eosin and immunohistochemically against connexin-43 to demonstrate gap junctions (intercalated discs). RESULTS: At 1 week the labeled cells were still undifferentiated, but early expression of connexin-43 could be detected at contact points between the implanted cells and the native myocytes. By 4 to 6 weeks, labeled, fully differentiated myocytes could be seen to interconnect among themselves and with native cardiomyocytes by means of intercalated discs. In sections parallel to the myofibers, full integration of new labeled myocytes with the native myofiber cells could be observed. Furthermore, the labeled myofibers were in parallel with the native, unlabeled fibers. We postulate that such supracellular structural integration was enhanced by fiber stretching during cardiac contractions, sending signals for cellular reorientation and incorporation, in which the cytoskeletal system may play an important role. CONCLUSION: We conclude that implanted precursor cells can be integrated into native myocardial structure so as to contribute to myocardial function. Direct cell-to-cell contact seems to be an important signaling mechanism, which has implications for cellular implantation strategies.

Animals↗
PubMed2003

Executive and visuospatial deficits in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome.

Although neuropsychological deficits have been reported in mitochondrial cytopathies, patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) have not been studied systematically using a comprehensive test battery. The aim of our study was to assess the range and extent of putative cognitive dysfunction in 22 patients with CPEO or KSS, and to compare cognitive performance of patients with healthy control subjects matched for age, sex and years of education. Genetic analysis of skeletal muscle tissue from 22 patients with CPEO or KSS included screening for mitochondrial DNA (mtDNA) point mutations (3243/8344) and mtDNA deletions. All patients were examined by a neuropsychological test battery covering verbal skills, verbal and visual memory, visuo-spatial perception, visual construction, attention, abstraction and flexibility, and Quality of Life. Molecular genetic analysis of mtDNA revealed single large-scale deletions in 15 out of 22 patients and the tRNA (Leu) A3243G point mutation in two out of 22 patients. In five out of 22 patients none of the frequently encountered mtDNA mutations could be detected. Neuropsychological testing did not reveal general intellectual deterioration, but specific cognitive deficits, particularly in visual construction, attention and abstraction/flexibility. Subgroup analysis of 15 patients with mtDNA deletions showed similar results when compared with the full group. In our series of patients with CPEO or KSS neuropsychological testing did not reveal signs that would suggest general intellectual decline or dementia, but provided evidence of specific focal neuropsychological deficits, suggesting particular impairment of visuospatial perception associated to parieto-occipital lobes and executive deficits associated to the prefrontal cortex.

Adult↗
PubMed2002

Peroxisome proliferator-activated receptor-gamma in the renal mesangium.

The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that are expressed in a variety of tissues, including the liver (PPARalpha), adipose tissue, vascular smooth muscle, the heart, skeletal muscle, and the kidney (PPARgamma). PPARdelta is expressed ubiquitously. The receptors function as transcription factors to regulate the expression of genes involved in lipid metabolism, cell growth and migration as well as insulin-mediated skeletal muscle glucose uptake. Although the mechanisms by which all these actions occur have not been completely worked out, ligands to these receptors function to improve lipid metabolism, insulin sensitivity, endothelial dysfunction and urinary albumin excretion in patients with diabetes. Thus PPARs appear to have enormous implications for the management of cardiovascular disease.

Animals↗
PubMed1997

Decreased [3H]ouabain binding sites in skeletal muscle of rats with chronic heart failure.

Abnormalities intrinsic to skeletal muscle are thought to contribute to decrements in exercise capacity found in individuals with chronic heart failure (CHF). Na+-K+-adenosinetriphosphatase (the Na+ pump) is essential for maintaining muscle excitability and contractility. Therefore, we investigated the possibility that the number and affinity of Na+ pumps in locomotor muscles of rats with CHF are decreased. Myocardial infarction (MI) was induced in 8 rats, and a sham operation was performed in 12 rats. The degree of CHF was assessed approximately 180 days after surgery. Soleus and plantaris muscles were harvested, and Na+ pumps were quantified by using a [3H]ouabain binding assay. At the time of muscle harvest, MI and sham-operated rats were similar in age (458 +/- 54 vs. 447 +/- 34 days old, respectively). Compared with their sham-operated counterparts, MI rats had a significant amount of heart failure, right ventricular-to-body weight ratio was greater (48%), and the presence of pulmonary congestion was suggested by an elevated lung-to-body weight ratio (29%). Left ventricular end-diastolic pressure was significantly increased in the MI rats (11 +/- 1 mmHg) compared with the sham-operated controls (1 +/- 1 mmHg). In addition, mean arterial blood pressure was lower in the MI rats compared with their control counterparts. [3H]ouabain binding sites were reduced 18% in soleus muscle (136 +/- 12 vs. 175 +/- 13 pmol/g wet wt, MI vs. sham, respectively) and 22% in plantaris muscle (119 +/- 12 vs. 147 +/- 8 pmol/g wet wt, MI vs. sham, respectively). The affinity of these [3H]ouabain binding sites was similar for the two groups. The relationship between the reduction in Na+ pump number and the reduced exercise capacity in individuals with CHF remains to be determined.

Animals↗
PubMed1996

Myocardial involvement is very frequent among patients affected with subclinical Becker's muscular dystrophy.

BACKGROUND: Several cases of Becker's muscular dystrophy (BMD) have been reported, which showed mild or subclinical skeletal muscle involvement with an overt dilated cardiomyopathy. Here, for the first time, a group of 28 patients with BMD who had a subclinical or benign myopathy have been studied through a thorough cardiological assessment. METHODS AND RESULTS: Each patient underwent ECG and echocardiographic examinations. Molecular analyses of the dystrophin gene and protein were performed. An unexpectedly high incidence of myocardial involvement was observed among patients affected with subclinical (72%) or benign (60%) BMD. The cardiac involvement appears to develop early from the right ventricle. Both the increase in left ventricular end-diastolic volume and the reduction in the ejection fraction appeared to be age related. Severe left ventricular dilation with reduced ejection fraction, which could be complicated by life-threatening arrhythmias, may occur. Contrary to previous reports, which indicated the involvement of 5'-end mutations in cardiomyopathies as a result of dystrophin gene alterations, this study shows that despite the apparent concentration of deletions in two regions (5'-end and exons 47 through 49), no general conclusions can be drawn regarding the involvement of specific gene mutations in the development of cardiomyopathy. CONCLUSIONS: Cardiomyopathy is the main clinical feature and complication in patients affected by subclinical or mild BMD. The cardiac manifestation is characterized by early right ventricular involvement and is later associated with left ventricular impairment. In mild BMD, myocardial damage may develop because the patients, who are unaware of a possible cardiac involvement, are still able to perform strenuous muscle exercise and, through pressure or volume overload, may induce mechanical stress, which is harmful for dystrophin-deficient myocardial cells.

Adolescent↗
PubMed1998

Histological and biochemical assessment of mitochondrial function in dermatomyositis.

OBJECTIVE: Mitochondrial dysfunction in idiopathic inflammatory myopathies (IIM) remains a controversial issue. The aim of the present study was to investigate the correlation between histological abnormalities and the biochemical function of the skeletal muscle mitochondria from patients with dermatomyositis (DM). METHOD: We evaluated 10 patients with a new diagnosis of DM and 15 healthy individuals, matched by age and gender. Muscle biopsy was routinely processed for histochemical studies and biochemical analysis of pure mitochondria. The percentages of ragged-red fibres (RRF), cytochrome c oxidase (COX)-negative fibres and succinic dehydrogenase (SDH) hyper-reactive fibres were calculated, oxygen utilization using different substrates was assessed polarographically, and enzymatic activity of individual complexes of the electron transport chain (ETC) and ATPase was measured spectrophotometrically. RESULTS: We found an increased percentage of COX-negative and SDH hyper-reactive fibres in DM patients (0.82 and 1.82%, respectively) compared to controls (0.26 and 0.22%; P < 0.05 and P = 0.001, respectively); however, oxidation rates of different substrates and enzymatic activities of ETC and ATPase did not differ significantly between both groups. CONCLUSION: The overall function of ETC from skeletal muscle mitochondria is not affected in DM.

Adenosine Triphosphatases↗
PubMedDate not supplied

[Biology of malignant hyperthermia: a disease of the calcium channels of the skeletal muscle].

Malignant hyperthermia susceptibility (MHS), a skeletal muscle disorder, is mostly inherited as an autosomal dominant trait. Exposure of susceptible individuals to volatile halogenated anaesthetics can lead to a MH episode resulting in irreversible tissue damages or to the patient's death if not immediately reversed by dantrolene treatment. A MH episode is characterised by a combination of hyperthermia, skeletal muscle rigidity and hypermetabolism. Porcine stress syndrome has proved to be a valuable model for physiopathological studies of MHS. Malignant hyperthermia syndrome is associated with a failure of the calcium homeostasis in muscular fibres. Dysfunction of the calcium channels: the ryanodine receptor (RyR) and the dihydropyridine receptor (DHPR), which are involved in the release of the Ca2+ stored in sarcoplasmic reticulum has been clearly demonstrated. A biochemical test based on the analysis of the in vitro contracture response of muscular fibres to caffeine and halothane was developed to define the MHS status of patients. Although the genetic analysis of MHS has beneficiated from recent progresses, genetic testing is still far to answer to all testing situations. If in swine, hyperthermia syndrome was always associated with a unique mutation of the RyR1 gene, genetic analysis is far more complicated in human: i) more than 20 different MHS mutations in the RyR1 gene have been described; ii) a mutation of the gene encoding the dihydropyridine receptor has been identified; iii) 4 other potential MHS loci have been reported.

Animals↗
PubMed2005

Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice.

Type 2 diabetes is a heterogeneous disease characterized by insulin resistance and altered glucose and lipid metabolism in multiple organs. To understand the complex series of events that occur during the development of obesity-associated diabetes, we examined the temporal pattern of changes in insulin action and glucose metabolism in individual organs during chronic high-fat feeding in C57BL/6 mice. Insulin-stimulated cardiac glucose metabolism was significantly reduced after 1.5 weeks of high-fat feeding, and cardiac insulin resistance was associated with blunted Akt-mediated insulin signaling and GLUT4 levels. Insulin resistance in skeletal muscle, adipose tissue, and liver developed in parallel after 3 weeks of high-fat feeding. Diet-induced whole-body insulin resistance was associated with increased circulating levels of resistin and leptin but unaltered adiponectin levels. High-fat feeding caused insulin resistance in skeletal muscle that was associated with significantly elevated intramuscular fat content. In contrast, diet-induced hepatic insulin resistance developed before a marked increase in intrahepatic triglyceride levels. Cardiac function gradually declined over the course of high-fat feeding, and after 20 weeks of high-fat diet, cardiac dysfunction was associated with mild hyperglycemia, hyperleptinemia, and reduced circulating adiponectin levels. Our findings demonstrate that cardiac insulin resistance is an early adaptive event in response to obesity and develops before changes in whole-body glucose homeostasis. This suggests that obesity-associated defects in cardiac function may not be due to insulin resistance per se but may be attributable to chronic alteration in cardiac glucose and lipid metabolism and circulating adipokines.

Adipose Tissue↗
PubMed1998

A novel approach for comparative study of periosteum, muscle, subcutis, and skin microcirculation by intravital fluorescence microscopy.

Herein, we report a new model, which allows comparative study of the microcirculation of different peripheral tissues, i.e., periosteum, skeletal muscle, subcutis, and skin. Using dextran-insensitive Wistar rats gracilis and semitendinosus muscles of the left hindlimb were prepared in association with their appertaining tibial fragments, subcutis, and skin. Blood supply was guaranteed by the femoral artery via the saphenous vessels. High-resolution intravital epi-illumination microscopy of the two muscles displayed the typical microvascular architecture with the capillaries running in parallel to each other (capillary density (CD) 128.4 +/- 4.5 cm-1). In subcutis and skin, capillaries were found arranged as interconnecting mesh-like networks with a density, which was significantly higher (P < 0.05) in subcutis (191.0 +/- 5.5 cm-1) compared with skin (108.9 +/- 3.3 cm-1). Analysis of periosteal tissue revealed two distinct types of arrangements of microvascular architecture. Adjacent to the major feeding and draining vessels of the periosteum, capillaries were organized in densely meshed shunt-like networks, revealing the highest capillary density (242.7 +/- 13.2 cm-1; P < 0.05) of all tissues studied. Periosteal capillaries distant from the major feeding and draining vessels were arranged in parallel to the longitudinal axis of the tibial bone and presented with a density similar to that of the skeletal muscle (128. 6 +/- 9.4 cm-1). Topical application of acetylcholine for analysis of physiological reactivity of the microvasculature showed dose-dependent arteriolar dilation. Moreover, a 3-min upstream femoral artery occlusion demonstrated an appropriate hyperemic response in all tissues studied, indicating intact myogenic control. A prolonged period of ischemia (120 min) followed by reperfusion (60 min) caused massive (P < 0.05) leukocyte-endothelial cell interaction in postcapillary venules, similarly as reported in other microvascular tissue preparations. We propose that the model presented provides a good approach to all peripheral tissues for both the analysis of the physiology of tissue-confined microvascular control and the development of novel therapeutic strategies to counteract manifestation of nutritional dysfunction and inflammatory response in disease.

Acetylcholine↗
PubMed2005

Impaired voluntary running capacity of creatine kinase-deficient mice.

The creatine kinase system (CK) is important for energy delivery in skeletal and cardiac muscles. The two main isoforms of this enzyme, cytosolic MM-CK and mitochondrial mi-CK, are expressed in a developmental and muscle-type specific manner. Mice deficient in one or both of these isoforms are viable and fertile but exhibit profound functional, metabolic and structural muscle remodelling that primarily affects fast skeletal muscles, which show an increased contribution of oxidative metabolism to contractile function. However, the consequences of these alterations in terms of physical capabilities have not yet been characterized. Consequently, we compared the voluntary exercise capacity of 9-month-old male wild-type (WT), M-CK knockout (M-CK(-/-)), and M-CK and mi-CK double knockout (CK(-/-)) mice, using cages equipped with running wheels. Exercise performance, calculated by total distance covered and by work done during the training period, was more than 10-fold lower in CK(-/-) mice than controls, with M-CK(-/-) mice exhibiting intermediate performance. Similarly, the mean distance run per activation was lower in M-CK(-/-) and even lower in CK(-/-) mice. However, the maximal running speed (V(max)) was lower only for CK(-/-) mice. This was accompanied by severe skeletal muscle mass decrease in CK(-/-) mice, with signs of histological damage that included enlarged interstitial areas, aggregations of mononuclear cells in the interstitium, heterogeneity of myofibre size and the presence of very small fibres. No overt sign of cardiac dysfunction was observed by magnetic resonance imaging during dobutamine stimulation. These results show that metabolic failure induced by CK deficiency profoundly affects the ability of mice to engage in chronic bouts of endurance running exercise and that this decrease in performance is also associated with muscle wasting.

Animals↗
PubMed1995

Preincubation of endotoxin with monoclonal anti-lipid A (E5), but not in vivo treatment, inhibits circulatory dysfunction.

Monoclonal antibodies (mAb) directed against the toxic lipid A portion of lipopolysaccharide (LPS) have been shown to bind lipid A in vitro, but clinical trials of such mAbs have yielded mixed results. In 53 rats instrumented for macrocirculatory and cremaster muscle microcirculatory measurements, we examined whether E5, a murine-derived anti-lipid A mAb, could inhibit LPS-induced circulatory dysfunction when incubated with LPS in vitro or given separately in vivo prior to LPS administration. Compared with Control rats (Group I), rats infused with 10 mg/kg Escherichia coli LPS (Group II) displayed marked decreases in arterial pressure and cardiac output and marked decreases in erythrocyte velocity in second, third, and fourth order skeletal muscle arterioles. Infusion of 2 mg/kg E5 90 min prior to LPS infusion (Group III) did not improve cardiovascular performance. In contrast, incubation of LPS with either 2 mg/kg (Group IV) or 10 mg/kg (Group V) E5 prior to infusion significantly attenuated LPS-induced changes in both macrocirculatory and microcirculatory function. Further investigation of the disparity between the in vitro and in vivo neutralizing capacity of anti-lipid A mAbs may aid interpretation of the variable clinical results achieved with these preparations.

Analysis of Variance↗
PubMed2001

Dendritic cells presenting pyruvate kinase M1/M2 isozyme peptide can induce experimental allergic myositis in BALB/c mice.

Polymyositis (PM) is an inflammatory muscle disease caused by autoimmune dysfunction, considered to be caused by cytotoxic CD8 T cells. To date, no autoantigens have been identified. We attempted to induce an experimental allergic myositis (EAM) in BALB/c mice by inoculating syngeneic dendritic cells (DC) presenting peptides that are expected to match the binding anchor motif of H-2K(d) (BALB/c). We selected peptides that are highly expressed in skeletal muscle. Only when we inoculated syngeneic bone marrow-derived DC presenting pyruvate kinase M1/M2 peptide 464-472 in BALB/c mice, 41.7% of the mice (EAM) developed pathological changes in skeletal muscle compatible to human PM. Under other conditions (when we inoculated DC presenting no synthetic peptides into BALB/c or C57BL/6 mice and DC presenting pyruvate kinase M1/M2 peptide into C57BL/6 mice), there were no necrotizing and inflammatory lesions. Induction of EAM in the same manner as above also induced CTL activity against P815 cells with the same peptide and syngeneic differentiated cultured myotubes without peptides by the chromium release assay. Consistent with the similarity of the binding anchor motif of H-2K(d) (BALB/c) and HLA A*2402, we conclude that pyruvate kinase M1/M2 peptide is a candidate autoantigen not only in BALB/c-EAM but also in human-PM with the HLA A*2402 allele.

Animals↗
PubMed1994

MRI assessment of the normal temporomandibular joint with the use of projective geometry.

A new analysis, the Projective Invariant Analysis, was developed for the evaluation of magnetic resonance images of the temporomandibular joint. This method was used because it takes into account factors such as linear and angular measurements that simple Euclidean geometric methods fail to address. Forty "normal" joints (20 subjects) and 65 "abnormal" joints were analyzed. Joints were defined as normal if they had a Class I skeletal pattern and a Class I occlusion. In addition, a history was obtained and a clinical examination was performed on each of these subjects to rule out any temporomandibular joint dysfunction, masticatory muscle myalgia, or cervicalgia. The images of the 40 normal joints were compared with 65 previously taken images of 53 patients with conditions that had been diagnosed as anteriorly displaced disks with reduction. These two groups were compared with the use of the analysis method described by Drace and Enzmann that uses angular measurements. The groups were also analyzed with the use of a new method in which the structural relationships of the articular eminence, gleniod fossa, mandibular condyle, and articular disk were related to each other using projective geometry. For the projective invariant analysis, a 95% confidence ellipse was constructed on the basis of the normal data. All but one of the 40 normal points fell within this ellipse, and only three of the 65 abnormal points were inside the ellipse. Both analyses showed a significant difference between the normal and abnormal groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

Apoptosis and aging: role of the mitochondria.

Apoptosis research is a rapidly developing area, but the role of apoptosis is still unclear and controversial. For example, several studies document a significant loss of cardiac and skeletal myocytes during normal aging, possibly by apoptotic mechanisms. This loss in cells may be directly mediated by mitochondrial dysfunction caused by chronic exposure to oxidants and increased activation of mitochondrial permeability transition pores. This review will discuss apoptosis in the context of normal aging of T cells, cardiac myocytes, skeletal muscle, and brain cortex. Particular attention is paid to the role of the mitochondria, because they have been implicated as a major control center regulating apoptosis. Mitochondrial oxidative stress and a decline in mitochondrial energy production in vitro often leads to activation of apoptotic pathways, but whether this occurs in vivo is unclear.

Aging↗
PubMed2006

Vascular and metabolic effects of candesartan: insights from therapeutic interventions.

BACKGROUND: Effects of angiotensin II type 1 receptor blockers (ARBs) to improve endothelial dysfunction may be due to mechanisms in addition to the reduction of high blood pressure per se. Endothelial dysfunction is characterized by vascular inflammation that contributes to clinically significant atherosclerosis and by an increased tendency for thrombus formation. Hypertensive patients have impaired endothelial functions that have positive predictive power with respect to future cardiovascular events. OBJECTIVES: The present review will focus on multiple mechanisms underlying vascular and metabolic effects of ARBs that may synergize to prevent or regress atherosclerosis, onset of diabetes, and coronary heart disease. CONCLUSIONS: Angiotensin II accelerates the development of atherosclerosis by activating angiotensin II type 1 receptors that then promote superoxide anion generation and oxidative stress, leading to activation of nuclear transcription factor and endothelial dysfunction. Activation of angiotensin II type 1 receptors also stimulates increased expression of plasminogen activator inhibitor type 1 and tissue factor. Endothelial dysfunction associated with the metabolic syndrome and other insulin-resistant states is characterized by impaired insulin-stimulated production of nitric oxide from the endothelium and decreased blood flow to skeletal muscle. Increasing insulin sensitivity therefore improves endothelial function, and this may be an additional mechanism whereby ARBs decrease the incidence of coronary heart disease and the onset of diabetes. Adiponectin serves to link obesity with insulin resistance. In addition, adiponectin has anti-atherogenic properties.

Adiponectin↗