Joseph Fomusi Ndisang

University of Saskatchewan, Saskatoon, Saskatchewan, Canada

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Publications (66)219.23 Total impact

  • Joseph Fomusi Ndisang
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    ABSTRACT: The incidence of cardiac complications such as myocardial infarction and congestive heart failure is increasing. Once congestive heart failure emerges, little can be done to improve long-term cardiac function. The cellular basis of this downward spiral may be the dramatic loss of viable cardiomyocytes following acute ischemia and/or chronic apoptosis/necrosis which are not adequately replaced. Contrary to the old postulates of developmental biology, tissue self-renewal is not limited to blood, intestines and skin, but other organs including the heart have some capabilities of self-renewal. However, the intrinsic ability of self-renewal of adult myocardium or cardiomyogenesis is limited and thus novel paradigms capable of potentiating this process of regenerative organogenesis should be sought. Several strategies and paradigms are being currently explored, and among these is the heme-oxygenase system. Emerging evidence indicate that the heme-oxygenase system could be explored in regenerative medicine given its unique ability to concomitantly suppress apoptosis and necrosis, while facilitating tissue regeneration/repair and the formation of new blood vessels. This review highlights the recent development of heme-oxygenase in myocardial repair and regeneration.
    No preview · Article · Dec 2015 · Frontiers in Bioscience
  • Shuchita Tiwari · Joseph Fomusi Ndisang

    No preview · Article · Dec 2015 · Canadian Journal of Diabetes
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    Joseph Fomusi Ndisang · Sharad Rastogi · Alfredo Vannacci

    Full-text · Article · Aug 2015 · Journal of Diabetes Research
  • Joseph Fomusi Ndisang
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    ABSTRACT: Acute and chronic kidney failure constitutes a major health issue. Renal complications including kidney failure occurs in all segments of the population including adolescents and children. The incidence of renal complications including kidney failure is on the rise. Moreover, with aging of the population and the high incidence of diabetes, hypertension and obesity, this trend may prevail. An important cytoprotective enzyme that has been shown to improve renal function is heme-oxygenase (HO). HO is known to abate apoptosis and necrosis, and improves cell vitality, which in turn, may enhance tissue regeneration. Consistently, HO has been shown to restore tissue morphology by potentiating potentiate proteins of repair/regeneration and promoting neovascularization. The formation of new tissue may replace damaged or dysfunctional tissue to preserve cellular integrity and function after injury. Emerging evidence indicate that HO-inducers improve kidney function in several models including, (i) streptozotocin-induced diabetic rats, (ii) Zucker-diabetic-fatty rats, (iii) Zucker-fatty rats, (iii) spontaneously hypertensive rats, (iv) uninephrectomized deoxycorticosterone-acetate hypertensive rats, and (v) Nω-nitro-l-arginine-methyl ester (L-NAME)-induced hypertensive rats. The mechanisms underlying the HO-mediated reno-protection include: (i) the restoration of renal morphology by enhancing proteins of regeneration, (ii) the potentiation of the HO-adiponectin-atrial natriuretic peptide axis, with corresponding suppression of oxidative/inflammatory insults and extracellular matrix/profibrotic factors, and (iii) the potentiation of podocyte cytoskeletal proteins such as nephrin, podocin, podocalyxin and CD2-associated-protein, which are fundamental for forming the glomerular filtration barrier that selectively allows small molecules to pass through but not large protein molecules. Thus, this review highlights the HO-adiponectin-atrial natriuretic peptide axis in renoprotection.
    No preview · Article · Aug 2015 · Current pharmaceutical design
  • Joseph Fomusi Ndisang · Rajni Chibbar
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    ABSTRACT: Although heme-oxygenase (HO) is cytoprotective, its effects on podocyte regulators like podocalyxin, podocin, CD2-associated protein (CD2AP) in renal dysfunction in N (ω)-nitro-l-arginine-methyl ester (l-NAME) hypertension are largely unclear. Hypertension was induced in normotensive Sprague Dawley rats by administering l-NAME for 4 weeks. Enzyme immunoassay, enzyme-linked immunosorbent, histology/morphology, spectrophotometry, and western immunoblotting were used. HO was enhanced with heme-arginate (HA) or inhibited with chromium mesoporphyrin (CrMP). Treatment with heme-arginate reduced several renal histo-pathological lesions including renal arteriolar thickening, glomerular abnormalities, tubular cast, tubular atrophy/fibrosis, and mononuclear cell infiltration in l-NAME-hypertensive rats. Similarly, HA abated the elevated levels of renal extracellular matrix/profibrotic proteins like collagen and fibronectin that deplete nephrin, a fundamental transmembrane protein that forms the scaffoldings of the podocyte slit diaphragm permitting small ions to filter, but not massive excretion of proteins, hence proteinuria. Correspondingly, HA enhanced the aberrant expression of nephrin alongside other important regulators of podocyte like podocalyxin, podocin, and CD2AP, and improved renal function by reducing albuminuria/proteinuria, while increasing creatinine clearance. The renoprotection by HA were accompanied by significant reduction of inflammatory/oxidative mediators including nuclear factor-kappaB, macrophage inflammatory protein-1-alpha, macrophage chemoattractant protein-1, tumor necrosis factor-alpha, interleukin (IL)-6, IL1β, 8-isoprostane, endothelin-1, and aldosterone. These were associated with increased levels of adiponectin, HO-1, HO activity, cyclic guanosine monophosphate, and atrial natriuretic peptide (ANP), whereas the HO inhibitor, CrMP annulled the renoprotection and exacerbated renal dysfunction. HA improves renal function by attenuating histopathological lesions, suppressing inflammatory/oxidative mediators, abating profibrotic/extracellular matrix proteins, and reducing albuminuria/proteinuria, while concomitantly potentiating the HO-adiponectin-ANP axis, enhancing nephrin, podocin, podocalyxin, CD2AP and increasing creatinine clearance. Our study underscores the benefit of potentiating the HO-adiponectin-ANP against nephropathy. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    No preview · Article · Dec 2014 · American Journal of Hypertension
  • Joseph Fomusi Ndisang · Shuchita Tiwari

    No preview · Article · Oct 2014 · Canadian Journal of Diabetes
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    Joseph Fomusi Ndisang · Sharad Rastogi · Alfredo Vannacci

    Full-text · Article · Sep 2014 · Research Journal of Immunology
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    Joseph Fomusi Ndisang · Shuchita Tiwari
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    ABSTRACT: Obesity and excessive inflammation/oxidative stress are pathophysiological forces associated with kidney dysfunction. Although we recently showed that heme-oxygenase (HO) improves renal functions, the mechanisms are largely unclear. Moreover, the effects of the HO-system on podocyte cytoskeletal proteins like podocin, podocalyxin, CD2-associated-protein (CD2AP) and proteins of regeneration/repair like beta-catenin, Oct3/4, WT1 and Pax2 in renal tissue from normoglycemic obese Zucker-fatty rats (ZFs) have not been reported.
    Preview · Article · Sep 2014
  • Joseph Fomusi Ndisang · Shuchita Tiwari
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    ABSTRACT: Oxidative stress and inflammation are implicated in tissue remodeling, hypertrophy, and organ malfunction. Since heme-oxygenase (HO) is a cytoprotective enzyme with effects against oxidative stress and inflammation, we investigated the effects of upregulating HO with hemin on adipocyte hypertrophy, proteins of repair/regeneration including beta-catenin, Oct3/4 and Pax2 as well as pro-fibrotic/remodeling proteins like osteopontin and transforming growth factor-beta (TGF-β) in pericardial adipose tissue from obese Zucker rats (ZRs). Treatment with hemin significantly reduced pericardial adipose tissue inflammation/oxidative stress, suppressed osteopontin and TGF-β, and attenuated pericardial adipocyte hypertrophy in obese ZRs. These were associated with enhanced expression of the stem/progenitor-cell marker cKit; the potentiation of several proteins of regeneration including beta-catenin, Oct3/4, Pax2; and improved pericardial adipocyte morphology. Interestingly, the amelioration of adipocyte hypertrophy in hemin-treated animals was accompanied by improved adipocyte function, evidenced by increased levels of pericardial adipose tissue adiponectin. Furthermore, hemin significantly reduced hypertriglyceridemia and hypercholesteromia in obese ZRs. The protective effects of hemin were accompanied by robust potentiation HO activity and the total antioxidant capacity, whereas the co-administration of hemin with the HO inhibitor, stannous mesoporphyrin abolished the effects of hemin. These data suggest that hemin improves pericardial adipocyte morphology and function by enhancing proteins of repair and regeneration, while concomitantly abating inflammatory/oxidative insults and suppressing extracellular-matrix/profibrotic and remodeling proteins. The reduction of hypertriglyceridemia, hypercholesteromia, pericardial adiposity, and pericardial adipocyte hypertrophy with corresponding improvement of adipocyte morphology/function in hemin-treated animals suggests that HO inducers may be explored for the design of novel remedies against cardiac complications arising from excessive adiposity.
    No preview · Article · Jul 2014 · Experimental Biology and Medicine
  • Joseph Fomusi Ndisang
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    ABSTRACT: Peroxisome-proliferator-activated-receptors (PPARs) are transcription factors belonging to the superfamily of nuclear receptors. The isoforms of PPAR include PPAR alpha, PPAR gamma and PPAR delta (also known as PPAR beta). Generally, PPARs potentiate insulin sensitivity, improve glucose/lipid metabolism, suppress inflammation/oxidative stress, attenuate excessive immune responses, regulate cell-growth and differentiation. Interestingly, agonists of PPAR gamma and PPAR alpha have been shown to upregulate the heme-oxygenase (HO)-system. Conversely, the HO-system also enhances PPAR alpha, and potentiates the expression and activity of PPAR gamma. Moreover, the HO-system and related products including bilirubin, biliverdin, carbon monoxide and ferritin have been shown to increase insulin sensitivity, improve glucose/lipid metabolism, suppress inflammation/oxidative stress, abate immune response, and modulate cell-growth/differentiation. Therefore, an intimate, reciprocal, stimulatory and synergistic relationship between PPAR-signaling and the HO-system can be envisaged in the regulation of physiological functions. Thus, both the HO-system and PPARs-signaling participate in fine-tuning similar physiological functions, so novel pharmacological agents capable of optimizing this interaction should be sought. The coordinated regulation of PPAR-signaling and the HO-system may constitute the basis for future drug design.
    No preview · Article · Jun 2014 · Frontiers in Bioscience
  • Joseph Fomusi Ndisang · Rajni Chibbar · Nina Lane
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    ABSTRACT: Heart failure and related cardiac complications remains a great health challenge. We investigated the effects of upregulating heme-oxygenase (HO) on myocardial histo-pathological lesions, proinflammatory cytokines/chemokines, oxidative mediators and important markers of heart failure such as osteopontin and osteoprotergerin in N(ω)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Treatment with the HO-inducer, heme-arginate improved myocardial morphology in L-NAME hypertensive rats by attenuating subendocardial injury, interstitial fibrosis, mononuclear-cell infiltration and cardiomyocyte hypertrophy. These were associated with the reduction of several inflammatory/oxidative mediators including chemokines/cytokines such as macrophage inflammatory protein-1 alpha (MIP-1α), macrophage chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, endothelin-1, 8-isoprostane, nitrotyrosine, and aldosterone. Similarly, heme-arginate abated the elevated levels of extracellular matrix/remodeling proteins including transforming-growth factor beta (TGF-β1) and collagen-IV in the myocardium. These were accompanied by significant reduction of proteins of heart failure such as osteopontin and osteoprotegerin. Interestingly, the cardio-protective effects of heme-arginate were associated with the potentiation of adiponectin, atrial-natriuretic peptide (ANP), HO-1, HO-activity, cyclic gnanosine monophosphate (cGMP) and the total-anti-oxidant capacity, whereas the HO-inhibitor, chromium-mesoporphyrin nullified the effects of heme-arginate, exacerbating inflammatory injury and oxidative insults. We conclude that heme-arginate therapy protects myocardial damage by potentiating the HO-adiponectin-ANP axis, which in turn suppressed the elevated levels of aldosterone, pro-inflammatory chemokines/cytokines, mononuclear-cell infiltration and oxidative stress, with concomitant reduction of extracellular matrix/remodeling proteins and heart failure proteins. These data suggest a cardio-protective role of the HO system against L-NAME-induced hypertension that could be explored in the design of novel strategies against cardiomyopathy.
    No preview · Article · Apr 2014 · European journal of pharmacology
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    Joseph Fomusi Ndisang · Sharad Rastogi · Alfredo Vannacci

    Full-text · Article · Mar 2014 · Journal of Diabetes Research
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    Joseph Fomusi Ndisang · Alfredo Vannacci · Sharad Rastogi

    Full-text · Article · Feb 2014 · Oxidative Medicine and Cellular Longevity
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    Joseph Fomusi Ndisang · Ashok Jadhav · Manish Mishra
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    ABSTRACT: The growing incidence of chronic kidney disease remains a global health problem. Obesity is a major risk factor for type-2 diabetes and renal impairment. Perirenal adiposity, by virtue of its anatomical proximity to the kidneys may cause kidney disease through paracrine mechanisms that include increased production of inflammatory cytokines. Although heme-oxygenase (HO) is cytoprotective, its effects on perirenal adiposity and diabetic nephropathy in Zucker-diabetic fatty rats (ZDFs) remains largely unclear. Upregulating the HO-system with hemin normalised glycemia, reduced perirenal adiposity and suppressed several pro-inflammatory/oxidative mediators in perirenal fat including macrophage-inflammatory-protein-1α (MIP-1α), endothelin (ET-1), 8-isoprostane, TNF-α, IL-6 and IL-1β. Furthermore, hemin reduced ED1, a marker of pro-inflammatory macrophage-M1-phenotype, but interestingly, enhanced markers associated with anti-inflammatory M2-phenotype such as ED2, CD206 and IL-10, suggesting that hemin selectively modulates macrophage polarization towards the anti-inflammatory M2-phenotype. These effects were accompanied by increased adiponectin, HO-1, HO-activity, atrial-natriuretic peptide (ANP), and its surrogate marker, urinary-cGMP. Furthermore, hemin reduced renal histological lesions and abated pro-fibrotic/extracellular-matrix proteins like collagen and fibronectin that deplete nephrin, an important transmembrane protein which forms the scaffolding of the podocyte slit-diaphragm allowing ions to filter but not massive excretion of proteins, hence proteinuria. Correspondingly, hemin increased nephrin expression in ZDFs, reduced markers of renal damage including, albuminuria/proteinuria, but increased creatinine-clearance, suggesting improved renal function. Conversely, the HO-blocker, stannous-mesoporphyrin nullified the hemin effects, aggravating glucose metabolism, and exacerbating renal injury and function. The hemin effects were less-pronounced in Zucker-lean controls with healthy status, suggesting greater selectivity of HO in ZDFs with disease. We conclude that the concomitant reduction of pro-inflammatory/oxidative mediators, macrophage infiltration and profibrotic/extracellular-matrix proteins, coupled to increased nephrin, adiponectin, ANP, cGMP and creatinine clearance may account for improved renal function in hemin-treated ZDFs. These findings suggest that HO-inducers like hemin may be explored against the co-morbidity of perirenal adiposity and diabetic nephropathy.
    Preview · Article · Jan 2014 · PLoS ONE
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    ABSTRACT: Although many obese individuals are normoglycemic and asymptomatic of cardiometabolic complications, this apparent healthy state may be a misnomer. Since heart failure is a major cause of mortality in obesity, we investigated the effects of heme-oxygenase (HO) on heart failure and cardiometabolic complications in obese normoglycemic Zucker-fatty rats (ZFs). Treatment with the HO-inducer, hemin, reduced markers of heart failure, such as osteopontin and osteoprotegerin, abated left-ventricular (LV) hypertrophy/fibrosis, extracellular matrix/profibrotic proteins including collagen IV, fibronectin, TGF-β1, and reduced cardiac lesions. Furthermore, hemin suppressed inflammation by abating macrophage chemoattractant protein-1, macrophage-inflammatory protein-1 alpha, TNF-α, IL-6, and IL-1β but enhanced adiponectin, atrial-natriuretic peptide (ANP), HO activity, insulin sensitivity, and glucose metabolism. Correspondingly, hemin improved several hemodynamic/echocardiographic parameters including LV-diastolic wall thickness, LV-systolic wall thickness, mean-arterial pressure, arterial-systolic pressure, arterial-diastolic pressure, LV-developed pressure, +dP/dt, and cardiac output. Contrarily, the HO-inhibitor, stannous mesoporphyrin nullified the hemin effect, exacerbating inflammatory/oxidative insults and aggravated insulin resistance (HOMA-index). We conclude that perturbations in insulin signaling and cardiac function may be forerunners to overt hyperglycemia and heart failure in obesity. Importantly, hemin improves cardiac function by suppressing markers of heart failure, LV hypertrophy, cardiac lesions, extracellular matrix/profibrotic proteins, and inflammatory/oxidative mediators, while concomitantly enhancing the HO-adiponectin-ANP axis.
    Preview · Article · Dec 2013 · Oxidative Medicine and Cellular Longevity
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    ABSTRACT: The prevalence of non-alcoholic fatty-liver disease (NAFLD) is increasing globally. NAFLD is a spectrum of related liver diseases that progressive from simple steatosis to serious complications like cirrhosis. The major pathophysiological driving of NAFLD includes elevated hepatic adiposity, increased hepatic triglycerides/cholesterol, excessive hepatic inflammation, and hepatocyte ballooning injury is a common histo-pathological denominator. Although heme-oxygenase (HO) is cytoprotective, its effects on hepatocyte ballooning injury have not been reported. We investigated the effects of upregulating HO with hemin or inhibiting it with stannous-mesoporphyrin (SnMP) on hepatocyte ballooning injury, hepatic adiposity and inflammation in Zucker-diabetic-fatty rats (ZDFs), an obese type-2-diabetic model. Hemin administration to ZDFs abated hepatic/plasma triglycerides and cholesterol, and suppressed several pro-inflammatory cytokines and chemokines including, TNF-α, IL-6, IL-1β, macrophage-inflammatory-protein-1α (MIP-1α) and macrophage-chemoattractant-protein-1 (MCP-1), with corresponding reduction of the pro-inflammatory M1-phenotype marker, ED1 and hepatic macrophage infiltration. Correspondingly, hemin concomitantly potentiated the protein expression of several markers of the anti-inflammatory macrophage-M2-phenotype including ED2, IL-10 and CD-206, alongside components of the HO-system including HO-1, HO-activity and cGMP, whereas the HO-inhibitor, SnMP abolished the effects. Furthermore, hemin attenuated liver histo-pathological lesions like hepatocyte ballooning injury and fibrosis, and reduced extracellular-matrix/profibrotic proteins implicated in liver injury such as osteopontin, TGF-β1, fibronectin and collagen-IV. We conclude that hemin restore hepatic morphology by abating hepatic adiposity, suppressing macrophage infiltration, inflammation and fibrosis. The selective enhancement of anti-inflammatory macrophage-M2-phenotype with parallel reduction of pro-inflammatory macrophage-M1-phenotype and related chemokines/cytokines like TNF-α, IL-6, IL-1β, MIP-1α and MCP-1 are among the multifaceted mechanisms by which hemin restore hepatic morphology.
    Preview · Article · Nov 2013 · PLoS ONE
  • Joseph Fomusi Ndisang · Ashok Jadhav
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    ABSTRACT: Diabetic nephropathy is characterized by elevated macrophage infiltration and inflammation. Although heme-oxygenase (HO) is cytoprotective, its role in macrophage infiltration and nephropathy in type-1 diabetes is not completely elucidated.Administering the HO-inducer, hemin to streptozotocin (STZ)-diabetic rats suppressed renal pro-inflammatory macrophage-M1-phenotype alongside several pro-inflammatory agents, chemokines and cytokines including macrophage-inflammatory-protein-1-alpha (MIP-1α), macrophage-chemoattractant-protein-1 (MCP-1), TNF-α, IL-1β, IL-6, NF-κB and aldosterone, a stimulator of the inflammatory/oxidative transcription factor, NF-κB. Similarly, hemin therapy attenuated extracellular-matrix/profibrotic proteins implicated in renal injury including fibronectin, collagen-IV and TGF-β1, and reduced several renal histo-pathological lesions such as glomerulosclerosis, tubular-necrosis, tubular-vacuolization and interstitial macrophage infiltration. Furthermore, hemin reduced markers of kidney dysfunction like proteinuria and albuminuria, but increased creatinine clearance, suggesting improved kidney function. Correspondingly, hemin significantly enhanced the anti-inflammatory macrophage-M2-phenotype, IL-10, adiponectin, HO-1, HO-activity and atrial-natriuretic-peptide (ANP), a substance that abates TNF-α, IL-6 and IL1β, with parallel increase of urinary-cGMP, a surrogate marker of ANP. Contrarily, co-administering the HO-inhibitor, chromium-mesoporphyrin (CrMP) with the HO-inducer, hemin nullified the anti-diabetic and renoprotective effects, whereas administering CrMP alone abrogated basal HO-activity, reduced basal adiponectin and ANP levels, aggravated hyperglycemia and further increased MCP-1, MIP-1α, aldosterone, NF-κB, TNF-α, IL-6, IL1β, proteinuria/albuminuria and aggravated creatinine clearance, thus exacerbated renal dysfunction, suggesting the importance of the basal HO-adiponectin-ANP axis in renoprotection and kidney function.Collectively, these data suggest that hemin ameliorates diabetic nephropathy by selectively enhancing the anti-inflammatory macrophage-M2-phenotype and IL-10, while concomitantly abating the pro-inflammatory macrophage-M1-phenotype and suppressing extracellular-matrix/profibrotic factors with reduction of renal lesions including interstitial macrophage infiltration. Since aldosterone stimulate NF-κB which activates cytokines like TNF-α, IL-6, IL-1β which in turn stimulate chemokines such as MCP-1 and MIP-1α to promote macrophage-M1-infiltration, the hemin-dependent potentiation of the HO-adiponectin-ANP axis may account for reduced macrophage infiltration and inflammatory insults in STZ-diabetic rats.
    No preview · Article · Oct 2013 · Endocrinology
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    Joseph Fomusi Ndisang · Sharad Rastogi

    Preview · Article · Oct 2013
  • Shuchita Tiwari · Joseph Fomusi Ndisang
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    ABSTRACT: The growing incidence of obesity and related complications such as cardiomyopathy and nephropathy remains a global health challenge. Many pathophysiological factors including inflammation, oxidative stress and endothelial dysfunction are implicated in obesity-induced abnormalities in the heart and kidney. Moreover, obesity and nutrient-overload are associated with the activation of different inflammatory/oxidative signaling pathways such as endoplasmic reticulum stress, nuclear factor-kappaB (NF-B), toll-like-receptor-4 (TLR4) and the renin-angiotensin-aldosterone system (RAAS). The pathophysiological role of RAAS, TLR4 and NF-B in perturbing physiological milieu is well acknowledged. Several pharmacological agents have been formulated to target one or more of these pathways. Although significant strides have been made in elucidating mechanisms implicated in obesity-related cardio-renal diseases, much still has to be done. The pathophysiology of cardiomyopathy and nephropathy is complex and multifaceted. Besides NF-B, TLR4, RAAS and inflammatory mediators such as cytokines and chemokines, a wide spectrum of different factors including, the environment, diets, lifestyles, genetics and epigenetics are also involved. With such multifactorial etiology, it remains a daunting challenge to identify the factor(s) that initiate the activation and propagation of adverse stimuli that eventually lead to cardiomyopathy and/or nephropathy in obese individuals. Similarly, the mechanisms of such activation and propagation should be clearly elucidated. Should these hurdles be overcome, there would be a greater likelihood for the development of more-effective therapeutic strategies for the prevention, treatment and management of obesity-induced cardiomyopathy and nephropathy. The present review examines the current state of knowledge and future directions of research in the area of obesity-related cardiomyopathy and nephropathy.
    No preview · Article · Jul 2013 · Current pharmaceutical design
  • Shuchita Tiwari · Joseph Fomusi Ndisang
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    ABSTRACT: Diabetes is a complex endocrine/metabolic disease with many related complications including micro-vascular and macro-vascular problems such as cardiomyopathy, nephropathy, neuropathy and retinopathy. Generally, type-1 diabetes is caused by autoimmune-mediated destruction of pancreatic beta cells leading to insulin deficiency. This is usually accompanied by dyslipidemia, enhanced hyperglycemia-mediated oxidative stress, endothelial-cell dysfunction and apoptosis. For decades, type-1 diabetes has been traditionally known as insulin-dependent, while type-2 as non-insulin dependent diabetes. However, it is becoming increasingly clear that insulin deficiency and insulin resistance are manifested in both forms of diabetes at different stages. Thus, it may be time revisit the nomenclature and adjust it to reflect these observations of insulin deficiency and insulin resistance in both forms of diabetes to avoid ambiguity when discussing forms of diabetes. Emerging evidence indicates that the heme-oxygenase (HO) system and related products including carbon monoxide, ferritin and biliverdin are capable of suppressing immune/inflammatory response, and abate oxidative stress and apoptosis. More importantly, upregulating the HO-system increases pancreatic beta-cell insulin release and reduce hyperglycemia in different diabetic models. Similarly, carbon monoxide, a product of the HO-catalyzed degradation of heme also enhances insulin production and improves glucose metabolism. Since excessive immune/inflammatory responses coupled to elevated apoptosis are among the cardinal pathophysiological features type-1 diabetes, this review highlights the role of the HO system and related products such as carbon monoxide and bilirubin in the modulation of apoptosis and immune response, and the beneficial effects of the HO-system in the pathogenesis of type-1 diabetes and related cardiometabolic complications.
    No preview · Article · Jul 2013 · Current pharmaceutical design