Emerging pathways of communication between the heart and non-cardiac organs

Abstract

The breakthrough discovery of cardiac natriuretic peptides provided the first direct demonstration of the connection between the heart and the kidneys for the maintenance of sodium and volume homeostasis in health and disease. Yet, little is still known about how the heart and other organs cross-talk. Here, we review three physiological mechanisms of communication linking the heart to other organs through: i) cardiac natriuretic peptides, ii) the microRNA-208a/mediator complex subunit-13 axis and iii) the matrix metalloproteinase-2 (MMP-2)/C-C motif chemokine ligand-7/cardiac secreted phospholipase A2 (sPLA2) axis – a pathway which likely applies to the many cytokines, which are cleaved and regulated by MMP-2. We also suggest experimental strategies to answer still open questions on the latter pathway. In short, we review evidence showing how the cardiac secretome influences the metabolic and inflammatory status of non-cardiac organs as well as the heart.

Keywords

heart / liver / metabolism / inflammation / natriuretic peptides / microRNA / matrix metalloproteinase

References

[1] GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013[J]. Lancet, 2015, 385(9963): 117–171.

[2] de Bold AJ, Borenstein HB, Veress AT, A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats[J]. Life Sci, 1981, 28(1): 89–94.

[3] de Bold AJ, Salerno TA. Natriuretic activity of extracts obtained from hearts of different species and from various rat tissues[J]. Can J Physiol Pharmacol, 1983, 61(2): 127–130.

[4] de Bold AJ, Flynn TG. Cardionatrin I- a novel heart peptide with potent diuretic and natriuretic properties[J]. Life Sci, 1983, 33(3): 297–302.

[5] Flynn TG, Davies PL, Kennedy BP, Alignment of rat cardionatrin sequences with the preprocardionatrin sequence from complementary DNA[J]. Science, 1985, 228(4697): 323–325.

[6] Grueter CE, van Rooij E, Johnson BA, A cardiac microRNA governs systemic energy homeostasis by regulation of MED13[J]. Cell, 2012, 149(3): 671–683.

[7] Berry E, Hernandez-Anzaldo S, Ghomashchi F, Matrix metalloproteinase-2 negatively regulates cardiac secreted phospholipase A2 to modulate inflammation and fever[J]. J Am Heart Assoc, 2015, 4(4): e001868.

[8] Hernandez-Anzaldo S, Berry E, Brglez V, Identification of a novel heart-liver axis: matrix metalloproteinase-2 negatively regulates cardiac secreted phospholipase A2 to modulate lipid metabolism and inflammation in the liver[J]. J Am Heart Assoc, 2015, 4(11): e002553.

[9] Wang X, Berry E, Hernandez-Anzaldo S, Matrix metalloproteinase-2 mediates a mechanism of metabolic cardioprotection consisting of negative regulation of the sterol regulatory element-binding protein-2/3-hydroxy-3-methylglutaryl-CoA reductase pathway in the heart[J]. Hypertension, 2015,65(4):882–888.

[10] Sudoh T, Kangawa K, Minamino N, A new natriuretic peptide in porcine brain[J]. Nature, 1988, 332(6159): 78–81.

[11] Nakamura S, Naruse M, Naruse K, Atrial natriuretic peptide and brain natriuretic peptide coexist in the secretory granules of human cardiac myocytes[J]. Am J Hypertens, 1991, 4(11): 909–912.

[12] Clerico A, Giannoni A, Vittorini S, Thirty years of the heart as an endocrine organ: physiological role and clinical utility of cardiac natriuretic hormones[J]. Am J Physiol Heart Circ Physiol, 2011, 301(1): H12–H20.

[13] Del Ry S, Cabiati M, Vozzi F, Expression of C-type natriuretic peptide and its receptor NPR-B in cardiomyocytes[J]. Peptides, 2011, 32(8): 1713–1718.

[14] Ogawa T, de Bold AJ. The heart as an endocrine organ[J]. Endocr Connect, 2014, 3(2): R31–R44.

[15] Sagnella GA. Measurement and significance of circulating natriuretic peptides in cardiovascular disease[J]. Clin Sci (Lond), 1998, 95(5): 519–529.

[16] Rademaker MT, Richards AM. Cardiac natriuretic peptides for cardiac health[J]. Clin Sci (Lond), 2005, 108(1): 23–36.

[17] Wei CM, Heublein DM, Perrella MA, Natriuretic peptide system in human heart failure[J]. Circulation, 1993, 88(3): 1004–1009.

[18] Del Ry S, Passino C, Maltinti M, C-type natriuretic peptide plasma levels increase in patients with chronic heart failure as a function of clinical severity[J]. Eur J Heart Fail, 2005, 7(7): 1145–1148.

[19] Mangat H, de Bold AJ. Stretch-induced atrial natriuretic factor release utilizes a rapidly depleting pool of newly synthesized hormone[J]. Endocrinology, 1993, 133(3): 1398–1403.

[20] Arvan P, Kuliawat R, Prabakaran D, Protein discharge from immature secretory granules displays both regulated and constitutive characteristics[J]. J Biol Chem, 1991, 266(22): 14171–14174.

[21] Gerzer R, Witzgall H, Tremblay J, Rapid increase in plasma and urinary cyclic GMP after bolus injection of atrial natriuretic factor in man. J Clin Endocrinol Metab, 1985, 61(6): 1217–1219.

[22] Lincoln TM, Cornwell TL. Intracellular cyclic GMP receptor proteins[J]. FASEB J, 1993, 7(2): 328–338.

[23] Melo LG, Steinhelper ME, Pang SC, ANP in regulation of arterial pressure and fluid-electrolyte balance: lessons from genetic mouse models[J]. Physiol Genomics, 2000, 3(1): 45–58.

[24] Vanderheyden M, Bartunek J, Goethals M. Brain and other natriuretic peptides: molecular aspects[J]. Eur J Heart Fail, 2004, 6(3): 261–268.

[25] Wiley KE, Davenport AP. Physiological antagonism of endothelin-1 in human conductance and resistance coronary artery[J]. Br J Pharmacol, 2001, 133(4): 568–574.

[26] Furuya M, Yoshida M, Hayashi Y, C-type natriuretic peptide is a growth inhibitor of rat vascular smooth muscle cells[J]. Biochem Biophys Res Commun, 1991, 177(3): 927–931.

[27] Franco-Saenz R, Atarashi K, Takagi M, Effect of atrial natriuretic factor on renin and aldosterone[J]. J Cardiovasc Pharmacol, 1989, 13(Suppl 6): S31–S35.

[28] Brenner BM, Ballermann BJ, Gunning ME, Diverse biological actions of atrial natriuretic peptide[J]. Physiol Rev, 1990, 70(3): 665–699.

[29] Burger AJ. A review of the renal and neurohormonal effects of B-type natriuretic peptide[J]. Congest Heart Fail, 2005, 11(1): 30–38.

[30] Sengenès C, Berlan M, De Glisezinski I, Natriuretic peptides: a new lipolytic pathway in human adipocytes[J]. FASEB J, 2000, 14(10): 1345–1351.

[31] Sengenes C, Stich V, Berlan M, Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women[J]. FASEB J, 2000, 14(10): 1345–1351.

[32] Sengenès C, Zakaroff-Girard A, Moulin A, Natriuretic peptide-dependent lipolysis in fat cells is a primate specificity[J]. Am J Physiol Regul Integr Comp Physiol, 2002, 283(1): R257–R265.

[33] Sengenes C, Bouloumie A, Hauner H, Involvement of a cGMP-dependent pathway in the natriuretic peptide-mediated hormone sensitive lipase phosphorylation in human adipocytes[J]. J Biol Chem, 2003, 278(49):48617–48626.

[34] Galitzky J, Sengenès C, Thalamas C, The lipid-mobilizing effect of atrial natriuretic peptide is unrelated to sympathetic nervous system activation or obesity in young men[J]. J Lipid Res, 2001, 42(4): 536–544.

[35] Sarzani R, Marcucci P, Salvi F, Angiotensin II stimulates and atrial natriuretic peptide inhibits human visceral adipocyte growth[J]. Int J Obes, 2008, 32(2): 259–267.

[36] Pierkes M, Gambaryan S, Bokník P, Increased effects of C-type natriuretic peptide on cardiac ventricular contractility and relaxation in guanylyl cyclase A-deficient mice[J]. Cardiovasc Res, 2002, 53(4): 852–861.

[37] Brusq JM, Mayoux E, Guigui L, Effects of C-type natriuretic peptide on rat cardiac contractility[J]. Br J Pharmacol, 1999, 128(1): 206–212.

[38] Beaulieu P, Cardinal R, Pagé P, Positive chronotropic and inotropic effects of C-type natriuretic peptide in dogs[J]. Am J Physiol, 1997, 273(4 Pt 2): H1933–H1940.

[39] Tokudome T, Horio T, Soeki T, Inhibitory effect of C-type natriuretic peptide (CNP) on cultured cardiac myocyte hypertrophy: interference between CNP and endothelin-1 signaling pathways[J]. Endocrinology, 2004, 145(5): 2131–2140.

[40] Santhekadur PK, Kumar DP, Seneshaw M, The multifaceted role of natriuretic peptides in metabolic syndrome[J]. Biomed Pharmacother, 2017, 92: 826–835.

[41] Schlueter N, de Sterke A, Willmes DM, Metabolic actions of natriuretic peptides and therapeutic potential in the metabolic syndrome[J]. Pharmacol Ther, 2014, 144(1): 12–27.

[42] Moro C. Natriuretic peptides and fat metabolism[J]. Curr Opin Clin Nutr Metab Care, 2013, 16(6): 645–649.

[43] Gruden G, Landi A, Bruno G. Natriuretic peptides, heart, and adipose tissue: new findings and future developments for diabetes research[J]. Diabetes Care, 2014, (11):2899–2908.

[44] Wang D, Oparil S, Feng JA, Effects of pressure overload on extracellular matrix expression in the heart of the atrial natriuretic peptide-null mouse[J]. Hypertension, 2003, 42(1): 88–95.

[45] Vellaichamy E, Khurana ML, Fink J, Involvement of the NF-kappa B/matrix metalloproteinase pathway in cardiac fibrosis of mice lacking guanylyl cyclase/natriuretic peptide receptor A[J]. J Biol Chem, 2005, 280(19): 19230–19242.

[46] Subramanian U, Kumar P, Mani I, Retinoic acid and sodium butyrate suppress the cardiac expression of hypertrophic markers and proinflammatory mediators in Npr1 gene-disrupted haplotype mice[J]. Physiol Genomics, 2016, 48(7): 477–490.

[47] Sarzani R, Salvi F, Dessì-Fulgheri P, Renin-angiotensin system, natriuretic peptides, obesity, metabolic syndrome, and hypertension: an integrated view in humans[J]. J Hypertens, 2008, 26(5): 831–843.

[48] Clerico A, Giannoni A, Vittorini S, The paradox of low BNP levels in obesity[J]. Heart Fail Rev, 2012, 17(1): 81– 96.

[49] Moro C. Targeting cardiac natriuretic peptides in the therapy of diabetes and obesity[J]. Expert Opin Ther Targets, 2016, 20(12): 1445–1452.

[50] Baskin KK, Grueter CE, Kusminski CM, MED13-dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver[J]. EMBO Mol Med, 2014, 6(12): 1610–1621.

[51] Lee JH, Bassel-Duby R, Olson EN. Heart- and muscle-derived signaling system dependent on MED13 and Wingless controls obesity in Drosophila[J]. Proc Natl Acad Sci USA, 2014, 111(26): 9491–9496.

[52] Konzer A, Ruhs A, Braun T, Global protein quantification of mouse heart tissue based on the SILAC mouse[J]. Methods Mol Biol, 2013, 1005: 39–52.

[53] Zanivan S, Krueger M, Mann M. In vivo quantitative proteomics: the SILAC mouse[J]. Methods Mol Biol, 2012, 757: 435–450.

[54] Gioia M, Foster LJ, Overall CM. Cell-based identification of natural substrates and cleavage sites for extracellular proteases by SILAC proteomics[J]. Methods Mol Biol, 2009, 539: 131–153.

[55] Ong SE, Blagoev B, Kratchmarova I, Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics[J]. Mol Cell Proteomics, 2002, 1(5): 376–386.

[56] Luther SA, Cyster JG. Chemokines as regulators of T cell differentiation[J]. Nat Immunol, 2001, 2(2): 102–107.

[57] White GE, Iqbal AJ, Greaves DR. CC chemokine receptors and chronic inflammation-therapeutic opportunities and pharmacological challenges[J]. Pharmacol Rev, 2013, 65(1): 47–89.

[58] Steinberg GR, Michell BJ, van Denderen BJ, Tumor necrosis factor alpha-induced skeletal muscle insulin resistance involves suppression of AMP-kinase signaling[J]. Cell Metab, 2006, 4(6): 465–474.

[59] Tse MCL, Herlea-Pana O, Brobst D, Tumor necrosis factor-alpha promotes phosphoinositide 3-kinase enhancer A and AMP-activated protein kinase interaction to suppress lipid oxidation in skeletal muscle[J]. Diabetes, 2017, 66(7): 1858–1870.

Acknowledgments

CFP is supported by a Natural Sciences and Engineering Council of Canada Discovery Grant and by funding from the University of Alberta Hospital Foundation for Medical Research. EHR was partially supported by a Visiting Scientist Fund from University of Alberta International.

RIGHTS & PERMISSIONS

2018 2018 by the Journal of Biomedical Research.