Cognitive impairment in heart failure: A protective role for angiotensin-(1-7)

Meredith Hay, Todd W Vanderah, Farmin Samareh-Jahani, Eleni Constantopoulos, Ajay R Uprety, Carol A Barnes, John Konhilas, Meredith Hay, Todd W Vanderah, Farmin Samareh-Jahani, Eleni Constantopoulos, Ajay R Uprety, Carol A Barnes, John Konhilas

Abstract

Patients with congestive heart failure (CHF) have increased hospital readmission rates and mortality if they are concomitantly diagnosed with cognitive decline and memory loss. Accordingly, we developed a preclinical model of CHF-induced cognitive impairment with the goal of developing novel protective therapies against CHF related cognitive decline. CHF was induced by ligation of the left coronary artery to instigate a myocardial infarction (MI). By 4- and 8-weeks post-MI, CHF mice had approximately a 50% and 70% decline in ejection fraction as measured by echocardiography. At both 4- and 8-weeks post-MI, spatial memory performance in CHF mice as tested using the Morris water task was significantly impaired as compared with sham. In addition, CHF mice had significantly worse performance on object recognition when compared with shams as measured by discrimination ratios during the novel object recognition NOR task. At 8-weeks post-MI, a subgroup of CHF mice were given Angiotensin (Ang)-(1-7) (50mcg/kg/hr) subcutaneously for 4 weeks. Following 3 weeks treatment with systemic Ang-(1-7), the CHF mice NOR discrimination ratios were similar to shams and significantly better than the performance of CHF mice treated with saline. Ang-(1-7) also improved spatial memory in CHF mice as compared with shams. Ang-(1-7) had no effect on cardiac function. Inflammatory biomarker studies from plasma revealed a pattern of neuroprotection that may underlie the observed improvements in cognition. These results demonstrate a preclinical mouse model of CHF that exhibits both spatial memory and object recognition dysfunction. Furthermore, this CHF-induced cognitive impairment is attenuated by treatment with systemic Ang-(1-7). (PsycINFO Database Record

(c) 2017 APA, all rights reserved).

Figures

Figure 1.
Figure 1.
Time-line for the course of the experiments for the two cohorts. See the online article for the color version of this figure.
Figure 2.
Figure 2.
Cardiac histology and morphometry in sham and congestive heart failure (CHF) mice. (A) Representative images of H&E stained hearts in longitudinal sections of sham and CHF mice. (B) Representative M-mode images of sham and MI mice treated with either saline or Ang-(1–7). From M-mode images, parameters of ventricular chamber dimensions and function were determined. See the online article for the color version of this figure.
Figure 3.
Figure 3.
Echocardiographic parameters of ventricular function and morphometry in sham and congestive heart failure (CHF) mice with and without Ang-(1–7). (A) LVIDs is lateral ventricular internal diameter at end-systole; (B) LVPWs is LV posterior wall thickness at end-systole; and (C) Percent ejection fraction (EF%). Data presented as mean ± S.E.M. Experimental group numbers are as follows, Sham + Saline, n = 5; Sham + Ang-(1–7), n = 7; MI + Saline, n = 8; MI + Ang-(1–7), n = 5. #p < .05 from baseline; #p < .05 from Sham group.)
Figure 4.
Figure 4.
Novel object recognition (NOR) task performance of sham and congestive heart failure (CHF) mice. (A) Mean discrimination ratios, taken from the first 2 min of “test phase” of CHF and sham mice 4-weeks post-MI. A positive score indicates more time spent with the novel object while a negative score indicates more time spent with the familiar object. A zero score indicates a null preference. CHF mice (n = 5) had significantly lower discriminations compared with shams (n = 5; −.43 ± .05 vs. +0.16 ± .1, F(1, 7) = 27.4, p = .001, ANOVA). * = p < .05. (B) Effects of Ang-(1–7) treatment on novel object recognition (NOR) task performance in CHF and sham mice. Following 3 weeks treatment with systemic Ang-(1–7), CHF mice (n = 6) NOR discrimination ratios were similar to shams (n = 3) and significantly greater than the CHF mice treated with saline (n = 4, * p < .05). CHF saline treated animals DRatios were significantly less that Sham animals (p < .05).
Figure 5.
Figure 5.
Total object exploration time similar in congestive heart failure (CHF) and Sham mice. Total time spent exploring the two identical objects was not different between the three groups suggesting (A) similar levels of interest in environment exploration. (B) During the familiarization phase with two identical objects, there was a null preference for the tw identical objects for CHF + Ang(1–7) mice, the CHF + saline mice and the Sham + Ang(1–7) mice (0.002 ± 0.03, −0.05 ± 0.02, 0.019 ± 0.05, respectively). These results suggest that there was no difference in object preference for identical objects during the familiarization phase.
Figure 6.
Figure 6.
Spatial version of the Morris water task performance of congestive heart failure (CHF) and sham mice. (A) Examples of swim paths for a sham and CHF mouse on Day 3 testing. The sham mouse, as seen in the upper plot, takes a significantly shorter path to the hidden platform compared with the CHF mouse (lower plot). (B) The mean corrected integrated path lengths (CIPL) for CHF (n = 10) and sham (n = 4) mice at 4-weeks post-MI. The paths taken by the CHF mice were significantly longer on Days 2, 3, and 4 compared with the sham group, * p < .05. These results suggest that CHF induces spatial memory loss. See the online article for the color version of this figure.
Figure 7.
Figure 7.
Reversal version of Morris water task performance of congestive heart failure (CHF) and sham mice. The mean corrected integrated path lengths (CIPL) for CHF (n = 10) and sham (n = 4) mice at 8-weeks post-MI. The CIPL in the CHF mice was significantly longer on Days 2 and 4 compared with the sham group. * p < .05.
Figure 8.
Figure 8.
Visual acuity and swim speed are similar in congestive heart failure (CHF) and sham mice tested with the Morris swim task. (A) There were no differences between the CHF and sham mice in ability to find the elevated platform suggesting that the visual acuity are the same in CHF and sham mice. (B) The average swim speed of the CHF (n = 10, filled histogram) and sham mice (n = 4, open histogram) 8-weeks postsurgery were similar.
Figure 9.
Figure 9.
Effects of Ang-(1–7) treatment on Morris swim task performance in congestive heart failure (CHF) and sham mice. The mean corrected integrated path lengths (CIPL) for CHF + Ang-(1–7) (n = 6), CHF + saline (n = 3), and sham + Ang-(1–7) (n = 4) mice 12-weeks post-MI. CHF + Ang-(1–7) mice (n = 6) showed significant improvement in spatial memory on the first day of the swim task and performed similarly to sham mice (n = 4), * p < .05 for CHF + Ang-(1–7) compared to CHF-saline and sham.
Figure 10.
Figure 10.
Effects of Ang-(1–7) treatment on serum inflammatory biomarkers in the 2nd Cohort. (A) CXCL12, (B) CXCL13, (C) CCL2, (D) IL-1ra, (E) G-CSF, (F) IL-16, (G) sICAM. * p < .05. See the online article for the color version of this figure.
Figure 11.
Figure 11.
Effects of Ang-(1–7) treatment on serum inflammatory biomarkers in early disease at 2-weeks post-MI and 1-week Ang-(1–7) treatment. (A) G-CSF, (B) IL1α, (C) IP10, (D) MIP1α, (E) MIP2. * p < .05. See the online article for the color version of this figure.

References

    1. Athilingam P, Moynihan J, Chen L, D’Aoust R, Groer M, & Kip K (2013). Elevated levels of interleukin 6 and C-reactive protein associated with cognitive impairment in heart failure. Congestive Heart Failure, 19, 92–98. 10.1111/chf.12007
    1. Aukrust P, Halvorsen B, Yndestad A, Ueland T, Øie E, Otterdal K, . . . Damås JK (2008). Chemokines and cardiovascular risk. Arteriosclerosis, Thrombosis, and Vascular Biology, 28, 1909–1919. 10.1161/ATVBAHA.107.161240
    1. Braunwald E (2008). Biomarkers in heart failure. The New England Journal of Medicine, 358, 2148–2159. 10.1056/NEJMra0800239
    1. Breckenridge R (2010). Heart failure and mouse models. Disease Models & Mechanisms, 3, 138–143. 10.1242/dmm.005017
    1. Burke SN, Maurer AP, Hartzell AL, Nematollahi S, Uprety A, Wallace JL, & Barnes CA (2012). Representation of three-dimensional objects by the rat perirhinal cortex. Hippocampus, 22, 2032–2044. 10.1002/hipo.22060
    1. Burke SN, Ryan L, & Barnes CA (2012). Characterizing cognitive aging of recognition memory and related processes in animal models and in humans. Frontiers in Aging Neuroscience, 4, 15 10.3389/fnagi.2012.00015
    1. Bussey TJ, Muir JL, & Aggleton JP (1999). Functionally dissociating aspects of event memory: The effects of combined perirhinal and postrhinal cortex lesions on object and place memory in the rat. The Journal of Neuroscience, 19, 495–502.
    1. Chapman KZ, Ge R, Monni E, Tatarishvili J, Ahlenius H, Arvidsson A, . . . Kokaia Z (2015). Inflammation without neuronal death triggers striatal neurogenesis comparable to stroke. Neurobiology of Disease, 83, 1–15. 10.1016/j.nbd.2015.08.013
    1. Clausen F, Hånell A, Björk M, Hillered L, Mir AK, Gram H, & Marklund N (2009). Neutralization of interleukin-1beta modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice. The European Journal of Neuroscience, 30, 385–396. 10.1111/j.1460-9568.2009.06820.x
    1. Conductier G, Blondeau N, Guyon A, Nahon JL, & Rovère C (2010). The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. Journal of Neuroimmunology, 224, 93–100. 10.1016/j.jneuroim.2010.05.010
    1. Dardiotis E, Giamouzis G, Mastrogiannis D, Vogiatzi C, Skoularigis J, Triposkiadis F, & Hadjigeorgiou GM (2012). Cognitive impairment in heart failure. Cardiology Research and Practice, 2012, 1–9. 10.1155/2012/595821
    1. Daulatzai MA (2016). Fundamental role of pan-inflammation and oxidative-nitrosative pathways in neuropathogenesis of Alzheimer’s disease. American Journal of Neurodegenerative Disease, 5, 1–28.
    1. Dénes A, Ferenczi S, Halász J, Környei Z, & Kovács KJ (2008). Role of CX3CR1 (fractalkine receptor) in brain damage and inflammation induced by focal cerebral ischemia in mouse. Journal of Cerebral Blood Flow and Metabolism, 28, 1707–1721. 10.1038/jcbfm.2008.64
    1. Dick SA, & Epelman S (2016). Chronic heart failure and inflammation: What do we really know? Circulation Research, 119, 159–176. 10.1161/CIRCRESAHA.116.308030
    1. Dimitrijevic OB, Stamatovic SM, Keep RF, & Andjelkovic AV (2007). Absence of the chemokine receptor CCR2 protects against cerebral ischemia/reperfusion injury in mice. Stroke, 38, 1345–1353. 10.1161/01.STR.0000259709.16654.8f
    1. Ennaceur A (2010). One-trial object recognition in rats and mice: Methodological and theoretical issues. Behavioural Brain Research, 215, 244–254. 10.1016/j.bbr.2009.12.036
    1. Ennaceur A, & Delacour J (1988). A new one-trial test for neurobiological studies of memory in rats. Behavioural Brain Research, 31, 47–59. 10.1016/0166-4328(88)90157-X
    1. Euston DR, Gruber AJ, & McNaughton BL (2012). The role of medial prefrontal cortex in memory and decision making. Neuron, 76, 1057–1070. 10.1016/j.neuron.2012.12.002
    1. Ferrario CM (2006). Angiotensin-converting enzyme 2 and angiotensin- (1–7): An evolving story in cardiovascular regulation. Hypertension, 47, 515–521. 10.1161/01.HYP.0000196268.08909.fb
    1. Gallagher M, Burwell R, & Burchinal M (1993). Severity of spatial learning impairment in aging: Development of a learning index for performance in the Morris water maze. Behavioral Neuroscience, 107, 618–626. 10.1037/0735-7044.107.4.618
    1. Gao XM, Dart AM, Dewar E, Jennings G, & Du XJ (2000). Serial echocardiographic assessment of left ventricular dimensions and function after myocardial infarction in mice. Cardiovascular Research, 45, 330–338. 10.1016/S0008-6363(99)00274-6
    1. Georgiadis D, Sievert M, Cencetti S, Uhlmann F, Krivokuca M, Zierz S, & Werdan K (2000). Cerebrovascular reactivity is impaired in patients with cardiac failure. European Heart Journal, 21, 407–413. 10.1053/euhj.1999.1742
    1. Gordon S (2008). Elie Metchnikoff: Father of natural immunity. European Journal of Immunology, 38, 3257–3264. 10.1002/eji.200838855
    1. Gruhn N, Larsen FS, Boesgaard S, Knudsen GM, Mortensen SA, Thomsen G, & Aldershvile J (2001). Cerebral blood flow in patients with chronic heart failure before and after heart transplantation. Stroke, 32, 2530–2533. 10.1161/hs1101.098360
    1. Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, . . . Woo YJ (2011). Forecasting the future of cardiovascular disease in the United States: A policy statement from the American Heart Association. Circulation, 123, 933–944. 10.1161/CIR.0b013e31820a55f5
    1. Hellner K, Walther T, Schubert M, & Albrecht D (2005). Angiotensin-(1–7) enhances LTP in the hippocampus through the G-protein-coupled receptor Mas. Molecular and Cellular Neurosciences, 29, 427–435.
    1. Helmy A, Guilfoyle MR, Carpenter KL, Pickard JD, Menon DK, & Hutchinson PJ (2016). Recombinant human interleukin-1 receptor antagonist promotes M1 microglia biased cytokines and chemokines following human traumatic brain injury. Journal of Cerebral Blood Flow and Metabolism, 36, 1434–1448. 10.1177/0271678X15620204
    1. Höcht C, Gironacci MM, Mayer MA, Schuman M, Bertera FM, & Taira CA (2008). Involvement of angiotensin-(1–7) in the hypothalamic hypotensive effect of captopril in sinoaortic denervated rats. Regulatory Peptides, 146, 58–66.
    1. Jefferson AL (2010). Cardiac output as a potential risk factor for abnormal brain aging. Journal of Alzheimer’s Disease, 20, 813–821.
    1. Jefferson AL, Himali JJ, Au R, Seshadri S, Decarli C, O’Donnell CJ, . . . Benjamin EJ (2011). Relation of left ventricular ejection fraction to cognitive aging (from the Framingham Heart Study). The American Journal of Cardiology, 108, 1346–1351. 10.1016/j.amjcard.2011.06.056
    1. Jiang T, Gao L, Shi J, Lu J, Wang Y, & Zhang Y (2013). Angiotensin-(1–7) modulates renin-angiotensin system associated with reducing oxidative stress and attenuating neuronal apoptosis in the brain of hypertensive rats. Pharmacological Research, 67, 84–93. 10.1016/j.phrs.2012.10.014
    1. Kass DA, Hare JM, & Georgakopoulos D (1998). Murine cardiac function: A cautionary tail. Circulation Research, 82, 519–522. 10.1161/01.RES.82.4.519
    1. Kesner RP, & Churchwell JC (2011). An analysis of rat prefrontal cortex in mediating executive function. Neurobiology of Learning and Memory, 96, 417–431. 10.1016/j.nlm.2011.07.002
    1. Kowarik MC, Cepok S, Sellner J, Grummel V, Weber MS, Korn T, . . . Hemmer B (2012). CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation. Journal of Neuroinflammation, 9, 93 10.1186/1742-2094-9-93
    1. Krumholz HM, Parent EM, Tu N, Vaccarino V, Wang Y, Radford MJ, & Hennen J (1997). Readmission after hospitalization for congestive heart failure among Medicare beneficiaries. Archives of Internal Medicine, 157, 99–104. 10.1001/archinte.1997.00440220103013
    1. Lazaroni TL, Raslan AC, Fontes WR, de Oliveira ML, Bader M, Alenina N, . . . Pereira GS (2012). Angiotensin-(1–7)/Mas axis integrity is required for the expression of object recognition memory. Neurobiology of Learning and Memory, 97, 113–123. 10.1016/j.nlm.2011.10.003
    1. Lazartigues E, Feng Y, & Lavoie JL (2007). The two fACEs of the tissue renin-angiotensin systems: Implication in cardiovascular diseases. Current Pharmaceutical Design, 13, 1231–1245. 10.2174/138161207780618911
    1. Lee VC, Lloyd EN, Dearden HC, & Wong K (2013). A systematic review to investigate whether angiotensin-(1–7) is a promising therapeutic target in human heart failure. International Journal of Peptides, 2013, 260346 10.1155/2013/260346
    1. Le Thuc O, Blondeau N, Nahon JL, & Rovere C (2015). The complex contribution of chemokines to neuroinflammation: Switching from beneficial to detrimental effects. Annals of the New York Academy of Sciences, 1351, 127–140. 10.1111/nyas.12855
    1. Le Thuc O, Cansell C, Bourourou M, Denis RG, Stobbe K, Devaux N, . . . Rovere C (2016). Central CCL2 signaling onto MCH neurons mediates metabolic and behavioral adaptation to inflammation. EMBO Reports, 17, 1738–1752. 10.15252/embr.201541499
    1. Liao X, Wang L, Yang C, He J, Wang X, Guo R, . . . Ma H (2011). Cyclooxygenase mediates cardioprotection of angiotensin-(1–7) against ischemia/reperfusion-induced injury through the inhibition of oxidative stress. Molecular Medicine Reports, 4, 1145–1150.
    1. Lindvall O, & Kokaia Z (2015). Neurogenesis following stroke affecting the adult brain. Cold Spring Harbor Perspectives in Biology, 7, a019034 10.1101/cshperspect.a019034
    1. Liu XS, Zhang ZG, Zhang RL, Gregg SR, Wang L, Yier T, & Chopp M (2007). Chemokine ligand 2 (CCL2) induces migration and differentiation of subventricular zone cells after stroke. Journal of Neuroscience Research, 85, 2120–2125. 10.1002/jnr.21359
    1. Lob HE, Schultz D, Marvar PJ, Davisson RL, & Harrison DG (2013). Role of the NADPH oxidases in the subfornical organ in angiotensin II-induced hypertension. Hypertension, 61, 382–387. 10.1161/HYPERTENSIONAHA.111.00546
    1. Mann DL (2015). Innate immunity and the failing heart: The cytokine hypothesis revisited. Circulation Research, 116, 1254–1268. 10.1161/CIRCRESAHA.116.302317
    1. Mao L, Huang M, Chen SC, Li YN, Xia YP, He QW, . . . Hu B (2014). Endogenous endothelial progenitor cells participate in neovascularization via CXCR4/SDF-1 axis and improve outcome after stroke. CNS Neuroscience & Therapeutics, 20, 460–468. 10.1111/cns.12238
    1. Marques FD, Melo MB, Souza LE, Irigoyen MC, Sinisterra RD, de Sousa FB, . . . Santos RA (2012). Beneficial effects of long-term administration of an oral formulation of angiotensin-(1–7) in infarcted rats. International Journal of Hypertension, 2012, 1–12. 10.1155/2012/795452
    1. Mecca AP, Regenhardt RW, O’Connor TE, Joseph JP, Raizada MK, Katovich MJ, & Sumners C (2011). Cerebroprotection by angiotensin-(1–7) in endothelin-1-induced ischaemic stroke. Experimental Physiology, 96, 1084–1096. 10.1113/expphysiol.2011.058578
    1. Moser MB, Moser EI, Forrest E, Andersen P, & Morris RG (1995). Spatial learning with a minislab in the dorsal hippocampus. Proceedings of the National Academy of Sciences of the United States of America, 92, 9697–9701. 10.1073/pnas.92.21.9697
    1. Mumby DG, Glenn MJ, Nesbitt C, & Kyriazis DA (2002). Dissociation in retrograde memory for object discriminations and object recognition in rats with perirhinal cortex damage. Behavioural Brain Research, 132, 215–226. 10.1016/S0166-4328(01)00444-2
    1. Mumby DG, & Pinel JP (1994). Rhinal cortex lesions and object recognition in rats. Behavioral Neuroscience, 108, 11–18. 10.1037/0735-7044.108.1.11
    1. Patel SK, Velkoska E, Freeman M, Wai B, Lancefield TF, & Burrell LM (2014). From gene to protein-experimental and clinical studies of ACE2 in blood pressure control and arterial hypertension. Frontiers in Physiology, 5, 227 10.3389/fphys.2014.00227
    1. Polizio AH, Gironacci MM, Tomaro ML, & Peña C (2007). Angiotensin-(1–7) blocks the angiotensin II-stimulated superoxide production. Pharmacological Research, 56, 86–90. 10.1016/j.phrs.2007.04.004
    1. Pullicino PM, Wadley VG, McClure LA, Safford MM, Lazar RM, Klapholz M, . . . Howard G (2008). Factors contributing to global cognitive impairment in heart failure: Results from a population-based cohort. Journal of Cardiac Failure, 14, 290–295. 10.1016/j.cardfail.2008.01.003
    1. Raizada MK, & Ferreira AJ (2007). ACE2: A new target for cardiovascular disease therapeutics. Journal of Cardiovascular Pharmacology, 50, 112–119. 10.1097/FJC.0b013e3180986219
    1. Redish AD, Battaglia FP, Chawla MK, Ekstrom AD, Gerrard JL, Lipa P, . . . Barnes CA (2001). Independence of firing correlates of anatomically proximate hippocampal pyramidal cells. The Journal of Neuroscience, 21, RC134.
    1. Regenhardt RW, Mecca AP, Desland F, Ritucci-Chinni PF, Ludin JA, Greenstein D, . . . Sumners C (2014). Centrally administered angiotensin-(1–7) increases the survival of stroke-prone spontaneously hypertensive rats. Experimental Physiology, 99, 442–453. 10.1113/expphysiol.2013.075242
    1. Ruscher K, Kuric E, Liu Y, Walter HL, Issazadeh-Navikas S, Englund E, & Wieloch T (2013). Inhibition of CXCL12 signaling attenuates the postischemic immune response and improves functional recovery after stroke. Journal of Cerebral Blood Flow and Metabolism, 33, 1225–1234. 10.1038/jcbfm.2013.71
    1. Saavedra JM, Sánchez-Lemus E, & Benicky J (2011). Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications. Psychoneuroendocrinology, 36, 1–18.
    1. Santos RA, Campagnole-Santos MJ, & Andrade SP (2000). Angiotensin-(1–7): An update. Regulatory Peptides, 91, 45–62. 10.1016/S0167-0115(00)00138-5
    1. Schneider A, Krüger C, Steigleder T, Weber D, Pitzer C, Laage R, . . . Schäbitz WR (2005). The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. The Journal of Clinical Investigation, 115, 2083–2098. 10.1172/JCI23559
    1. Solaroglu I, Cahill J, Tsubokawa T, Beskonakli E, & Zhang JH (2009). Granulocyte colony-stimulating factor protects the brain against experimental stroke via inhibition of apoptosis and inflammation. Neurological Research, 31, 167–172. 10.1179/174313209X393582
    1. Soriano SG, Amaravadi LS, Wang YF, Zhou H, Yu GX, Tonra JR, . . . Pan Y (2002). Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury. Journal of Neuroimmunology, 125, 59–65. 10.1016/S0165-5728(02)00033-4
    1. Sugiyama Y, Yagita Y, Oyama N, Terasaki Y, Omura-Matsuoka E, Sasaki T, & Kitagawa K (2011). Granulocyte colony-stimulating factor enhances arteriogenesis and ameliorates cerebral damage in a mouse model of ischemic stroke. Stroke, 42, 770–775. 10.1161/STROKEAHA.110.597799
    1. Tehranian R, Andell-Jonsson S, Beni SM, Yatsiv I, Shohami E, Bartfai T, . . . Iverfeldt K (2002). Improved recovery and delayed cytokine induction after closed head injury in mice with central overexpression of the secreted isoform of the interleukin-1 receptor antagonist. Journal of Neurotrauma, 19, 939–951. 10.1089/089771502320317096
    1. Ueland T, Gullestad L, Nymo SH, Yndestad A, Aukrust P, & Askevold ET (2015). Inflammatory cytokines as biomarkers in heart failure. Clinica Chimica Acta, 443, 71–77. 10.1016/j.cca.2014.09.001
    1. van Twist DJ, Houben AJ, de Haan MW, Mostard GJ, Kroon AA, & de Leeuw PW (2013). Angiotensin-(1–7)-induced renal vasodilation in hypertensive humans is attenuated by low sodium intake and angiotensin II co-infusion. Hypertension, 62, 789–793. 10.1161/HYPERTENSIONAHA.113.01814
    1. Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J, . . . Tummino P (2002). Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. The Journal of Biological Chemistry, 277, 14838–14843. 10.1074/jbc.M200581200
    1. Vilar-Bergua A, Riba-Llena I, Nafría C, Bustamante A, Llombart V, Delgado P, & Montaner J (2016). Blood and CSF biomarkers in brain subcortical ischemic vascular disease: Involved pathways and clinical applicability. Journal of Cerebral Blood Flow and Metabolism, 36, 55–71.
    1. Vogels RL, Scheltens P, Schroeder-Tanka JM, & Weinstein HC (2007). Cognitive impairment in heart failure: A systematic review of the literature. European Journal of Heart Failure, 9, 440–449. 10.1016/j.ejheart.2006.11.001
    1. Vorhees CV, & Williams MT (2006). Morris water maze: Procedures for assessing spatial and related forms of learning and memory. Nature Protocols, 1, 848–858. 10.1038/nprot.2006.116
    1. Wang Y, Qian C, Roks AJ, Westermann D, Schumacher SM, Escher F, . . . Walther T (2010). Circulating rather than cardiac angiotensin-(1–7) stimulates cardioprotection after myocardial infarction. Circulation: Heart Failure, 3, 286–293. 10.1161/CIRCHEARTFAILURE.109.905968
    1. Wilson WL, Munn C, Ross RC, Harding JW, & Wright JW (2009). The role of the AT4 and cholinergic systems in the nucleus basalis magnocellularis (NBM): Effects on spatial memory. Brain Research, 1272, 25–31. 10.1016/j.brainres.2009.03.025
    1. Winters BD, Saksida LM, & Bussey TJ (2008). Object recognition memory: Neurobiological mechanisms of encoding, consolidation and retrieval. Neuroscience and Biobehavioral Reviews, 32, 1055–1070. 10.1016/j.neubiorev.2008.04.004
    1. Woo MA, Kumar R, Macey PM, Fonarow GC, & Harper RM (2009). Brain injury in autonomic, emotional, and cognitive regulatory areas in patients with heart failure. Journal of Cardiac Failure, 15, 214–223. 10.1016/jxardfail.2008.10.020
    1. Woo MA, Macey PM, Fonarow GC, Hamilton MA, & Harper RM (2003). Regional brain gray matter loss in heart failure. Journal of Applied Physiology, 95, 677–684. 10.1152/jappl-physiol.00101.2003
    1. Wu JR, Moser DK, Lennie TA, Peden AR, Chen YC, & Heo S (2008). Factors influencing medication adherence in patients with heart failure. Heart & Lung, 37, 8–16. 10.1016/j.hrtlng.2007.02.003
    1. Xu P, Sriramula S, & Lazartigues E (2011). ACE2/ANG-(1–7)/Mas pathway in the brain: The axis of good. American Journal of Physiology Regulatory, Integrative and Comparative Physiology, 300, R804–R817. 10.1152/ajpregu.00222.2010
    1. Yirmiya R, & Goshen I (2011). Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain, Behavior, and Immunity, 25, 181–213. 10.1016/j.bbi.2010.10.015
    1. Young D, O’Neill K, Jessell T, & Wigler M (1988). Characterization of the rat mas oncogene and its high-level expression in the hippocampus and cerebral cortex of rat brain. Proceedings of the National Academy of Sciences of the United States of America, 85, 5339–5342. 10.1073/pnas.85.14.5339
    1. Zimmerman MC (2011). Angiotensin II and angiotensin-1–7 redox signaling in the central nervous system. Current Opinion in Pharmacology, 11, 138–143. 10.1016/jxoph.2011.01.001
    1. Zubcevic J, Waki H, Raizada MK, & Paton JF (2011). Autonomic-immune-vascular interaction: An emerging concept for neurogenic hypertension. Hypertension, 57, 1026–1033. 10.1161/HYPERTENSIONAHA.111.169748
    1. Zuccalà G, Marzetti E, Cesari M, Lo Monaco MR, Antonica L, Cocchi A, & Bernabei R (2005). Correlates of cognitive impairment among patients with heart failure: Results of a multicenter survey. American Journal of Medicine, 118, 496–502.
    1. Zuccalà G, Onder G, Pedone C, Carosella L, Pahor M, Bernabei R, & Cocchi A (2001). Hypotension and cognitive impairment: Selective association in patients with heart failure. Neurology, 57, 1986–1992. 10.1212/WNL.57.11.1986

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren