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Pituitary
Published in: Pituitary 4/2012

Open Access 01-12-2012

Microcirculation and atherothrombotic parameters in prolactinoma patients: a pilot study

Authors: Anne Q. Reuwer, Brigitte M. Sondermeijer, Suzanne Battjes, Rogier van Zijderveld, Danka J. F. Stuijver, Peter H. Bisschop, Marcel Th. B. Twickler, Joost C. M. Meijers, Reinier O. Schlingemann, Erik S. Stroes

Published in: Pituitary | Issue 4/2012

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Abstract

Atherothrombosis is a multifactorial process, governed by an interaction between the vessel wall, hemodynamic factors and systemic atherothrombotic risk factors. Recent in vitro, human ex vivo and animal studies have implicated the hormone prolactin as an atherothrombotic mediator. To address this issue, we evaluated the anatomy and function of various microvascular beds as well as plasma atherothrombosis markers in patients with elevated prolactin levels. In this pilot study, involving 10 prolactinoma patients and 10 control subjects, sidestream dark field (SDF) imaging revealed a marked perturbation of the sublingual microcirculation in prolactinoma patients compared to control subjects, as attested to by significant changes in microvascular flow index (2.74 ± 0.12 vs. 2.91 ± 0.05, respectively; P = 0.0006), in heterogeneity index (0.28 [IQR 0.18–0.31] vs. 0.09 [IQR 0.08–0.17], respectively; P = 0.002) and lower proportion of perfused vessels (90 ± 4.0% vs. 95 ± 3.0%, respectively; P = 0.016). In the retina, fluorescein angiography (FAG) confirmed these data, since prolactinoma patients more often have dilatated perifoveal capillaries. In plasma, prolactinoma patients displayed several pro-atherogenic disturbances, including a higher endogenous thrombin potential and prothrombin levels as well as decreased HDL-cholesterol levels. Prolactinoma patients are characterized by microvascular dysfunction as well as plasma markers indicating a pro-atherothrombotic state. Further studies are required to assess if prolactin is causally involved in atherothrombotic disease.
Literature
1.
2.
Lee KW, Lip GY (2003) Acute coronary syndromes: Virchow’s triad revisited. Blood Coagul Fibrinolysis 14:605–625CrossRefPubMed
3.
van Zaane B, Reuwer A, Büller H, Kastelein J, Gerdes V, Twickler M (2009) Hormones and cardiovascular disease: a shift in paradigm with clinical consequences? Semin Thromb Hemost 35:478–487CrossRefPubMed
4.
Ben-Jonathan N, LaPensee CR, LaPensee EW (2008) What can we learn from rodents about prolactin in humans? Endocr Rev 29:1–41CrossRefPubMed
5.
Reuwer AQ, van Eijk M, Houttuijn-Bloemendaal FM, van der Loos CM, Claessen N, Teeling P, Kastelein JJP, Hamann J, Goffin V, von der Thusen JH, Twickler M, Aten J (2011) The prolactin receptor is expressed in macrophages within human carotid atherosclerotic plaques: a role for prolactin in atherogenesis? J Endocrinol 208:107–117CrossRefPubMed
6.
Chavez-Rueda K, Hérnandéz J, Zenteno E, Leaños-Miranda A, Legorreta-Haquet MV, Blanco-Favela F (2005) Identification of prolactin as a novel immunomodulator on the expression of co-stimulatory molecules and cytokine secretions on T and B human lymphocytes. Clin Immunol 116:182–191CrossRefPubMed
7.
Montes de Oca P, Macotela Y, Nava G, Lopez-Barrera F, de la Escalera GM, Clapp C (2005) Prolactin stimulates integrin-mediated adhesion of circulating mononuclear cells to endothelial cells. Lab Invest 85:633–642CrossRefPubMed
8.
Levi M, van der Poll T, Buller HR (2004) Bidirectional relation between inflammation and coagulation. Circulation 109:2698–2704CrossRefPubMed
9.
Grosdemouge I, Bachelot A, Lucas A, Baran N, Kelly P, Binart N (2003) Effects of deletion of the prolactin receptor on ovarian gene expression. Reprod Biol Endocrinol 1:12CrossRefPubMed
10.
Ko JY, Ahn YL, Cho BN (2003) Angiogenesis and white blood cell proliferation induced in mice by injection of a prolactin-expressing plasmid into muscle. Mol Cells 15:262–267PubMed
11.
Struman I, Bentzien F, Lee H, Mainfroid V, D’Angelo G, Goffin V, Weiner RI, Martial JA (1999) Opposing actions of intact and N-terminal fragments of the human prolactin/growth hormone family members on angiogenesis: an efficient mechanism for the regulation of angiogenesis. Proc Natl Acad Sci USA 96:1246–1251CrossRefPubMed
12.
Molinari C, Grossini E, Mary DASG, Uberti F, Ghigo E, Ribichini F, Surico N, Vacca G (2007) Prolactin induces regional vasoconstriction through the {beta}2-adrenergic and nitric oxide mechanisms. Endocrinology 148:4080–4090CrossRefPubMed
13.
Le Moli R, Endert E, Fliers E, Mulder T, Prummel MF, Romijn JA, Wiersinga WM (1999) Establishment of reference values for endocrine tests II: hyperprolactinemia. Neth J Med 55:71–75CrossRefPubMed
14.
Hemker HC, Giesen P, Al Dieri R, Regnault V, de Smedt E, Wagenvoord R, Lecompte T, Béguin S (2003) Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 33:4–15CrossRefPubMed
15.
Trzeciak S, Dellinger RP, Parrillo JE, Guglielmi M, Bajaj J, Abate NL, Arnold RC, Colilla S, Zanotti S, Hollenberg SM (2007) Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival. Ann Emerg Med 49:88–98CrossRefPubMed
16.
De Backer D, Hollenberg S, Boerma C, Goedhart P, Büchele G, Ospina-Tascon G, Dobbe I, Ince C (2007) How to evaluate the microcirculation: report of a round table conference. Crit Care 11:R101CrossRefPubMed
17.
Klyscz T, Jünger M, Jung F, Zeintl H (1997) Cap image–a new kind of computer-assisted video image analysis system for dynamic capillary microscopy. Biomed Tech (Berl) 42:168–175CrossRef
18.
Spronk PE, Ince C, Gardien MJ, Mathura KR, Straaten HMO, Zandstra DF (2002) Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet 360:1395–1396CrossRefPubMed
19.
Hemker HC, Béguin S (1995) Thrombin generation in plasma: its assessment via the endogenous thrombin potential. Thromb Haemost 74:134–138PubMed
20.
Hemker HC, Al Dieri R, De Smedt E, Béguin S (2006) Thrombin generation, a function test of the haemostatic-thrombotic system. Thromb Haemost 96:553–561PubMed
21.
Nishino Y (1979) Hormonal control of prothrombin synthesis in rat liver microsomes, with special reference to the role of estradiol, testosterone and prolactin. Arch Toxicol Suppl 2:397–402CrossRefPubMed
22.
23.
Erem C, Kocak M, Nuhoglu I, Yilmaz M, Ucuncu O (2010) Blood coagulation, fibrinolysis and lipid profile in patients with prolactinoma. Clin Endocrinol 73:502–507
24.
Dorshkind K, Horseman ND (2000) The Roles of Prolactin, Growth Hormone, Insulin-Like Growth Factor-I, and Thyroid Hormones in Lymphocyte Development and Function: Insights from Genetic Models of Hormone and Hormone Receptor Deficiency. Endocr Rev 21:292–312CrossRefPubMed
25.
Schuett H, Luchtefeld M, Grothusen C, Grote K, Schieffer B (2009) How much is too much? Interleukin-6 and its signalling in atherosclerosis. Thromb Haemost 102:215–222PubMed
26.
Nishida H, Horio T, Suzuki Y, Iwashima Y, Tokudome T, Yoshihara F, Nakamura S, Kawano Y (2011) Interleukin-6 as an independent predictor of future cardiovascular events in high-risk Japanese patients: comparison with C-reactive protein. Cytokine 53:342–346CrossRefPubMed
27.
Friedrich N, Schneider HJ, Spielhagen C, Markus MRP, Haring R, Grabe HJ, Buchfelder M, Wallaschofski H, Nauck M (2011) The association of serum prolactin concentration with inflammatory biomarkers—cross-sectional findings from the population-based Study of Health in Pomerania. Clinical Endocrinology 2011 (Epub ahead of print)
28.
Zellweger R, Zhu XH, Wichmann MW, Ayala A, De Maso CM, Chaudry IH (1996) Prolactin administration following hemorrhagic shock improves macrophage cytokine release capacity and decreases mortality from subsequent sepsis. J Immunol 157:5748–5754PubMed
29.
Serri O, Li L, Mamputu JC, Beauchamp MC, Maingrette F, Renier G (2006) The influences of hyperprolactinemia and obesity on cardiovascular risk markers: effects of cabergoline therapy. Clin Endocrinol 64:366–370
30.
Yavuz D, Deyneli O, Akpinar I, Yildiz E, Gozu H, Sezgin O, Haklar G, Akalin S (2003) Endothelial function, insulin sensitivity and inflammatory markers in hyperprolactinemic pre-menopausal women. Eur J Endocrinol 149:187–193CrossRefPubMed
31.
Heshmati HM, Turpin G, de Gennes JL (1987) Chronic hyperprolactinemia and plasma lipids in women. Klin Wochenschr 65:516–519CrossRefPubMed
32.
Pelkonen R, Nikkilä EA, Grahne B (1982) Serum lipids, postheparin plasma lipase activities and glucose tolerance in patients with prolactinoma. Clin Endocrinol (Oxf) 16:383–390CrossRef
33.
Berinder K, Nyström T, Höybye C, Hall K, Hulting AL (2010) Insulin sensitivity and lipid profile in prolactinoma patients before and after normalization of prolactin by dopamine agonist therapy. Pituitary 3:199–207
34.
Haas MJ, Mooradian AD (2010) Regulation of high-density lipoprotein by inflammatory cytokines: establishing links between immune dysfunction and cardiovascular disease. Diabetes Metab Res Rev 26:90–99CrossRefPubMed
35.
Hermsdorff H, Zulet M, Puchau B, Martínez JA (2011) Central adiposity rather than total adiposity measurements are specifically involved in the inflammatory status from healthy young adults. Inflammation 34:161–170CrossRefPubMed
36.
Reaven PD, Emanuele N, Moritz T, Klein R, Davis M, Glander K, Duckworth W, Abraira C (2008) Proliferative diabetic retinopathy in type 2 diabetes is related to coronary artery calcium in the veterans affairs diabetes trial (VADT). Diabetes Care 31:952–957CrossRefPubMed
37.
Wong TY, Klein R, Couper DJ, Cooper LS, Shahar E, Hubbard LD, Wofford MR, Sharrett AR (2001) Retinal microvascular abnormalities and incident stroke: the atherosclerosis risk in communities study. Lancet 358:1134–1140CrossRefPubMed
38.
Savage HI, Hendrix JW, Peterson DC, Young H, Wilkinson CP (2004) Differences in pulsatile ocular blood flow among three classifications of diabetic retinopathy. Invest Ophthalmol Vis Sci 45:4504–4509CrossRefPubMed
39.
Georgiopoulos GA, Stamatelopoulos KS, Lambrinoudaki I, Lykka M, Kyrkou K, Rizos D, Creatsa M, Christodoulakos G, Alevizaki M, Sfikakis PP, Papamichael C (2009) Prolactin and preclinical atherosclerosis in menopausal women with cardiovascular risk factors. Hypertension 54:98–105CrossRefPubMed
40.
Ricken AM, Traenkner A, Merkwitz C, Hummitzsch K, Grosche J, Spanel-Borowski K (2007) The short prolactin receptor predominates in endothelial cells of micro- and macrovascular origin. J Vasc Res 44:19–30CrossRefPubMed
41.
Sauro MD, Zorn NE (1991) Prolactin induces proliferation of vascular smooth muscle cells through a protein kinase C-dependent mechanism. J Cell Physiol 148:133–138CrossRefPubMed
42.
Hirano K, Hirano M, Kanaide H (2004) Regulation of myosin phosphorylation and myofilament Ca2 + sensitivity in vascular smooth muscle. J Smooth Muscle Res 40:219–236CrossRefPubMed
43.
44.
Delaey C, Van de Voorde J (2000) Regulatory mechanisms in the retinal and choroidal circulation. Ophthalmic Res 32:249–256CrossRefPubMed
45.
Patton N, Aslam T, MacGillivray T, Pattie A, Deary IJ, Dhillon B (2005) Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures. J Anat 206:319–348CrossRefPubMed
46.
Bosch MM, Merz TM, Barthelmes D, Petrig BL, Truffer F, Bloch KE, Turk A, Maggiorini M, Hess T, Schoch OD, Hefti U, Sutter FK, Pichler J, Huber A, Landau K (2009) New insights into ocular blood flow at very high altitudes. J Appl Physiol 106:454–460CrossRefPubMed
47.
Mitchell P, Wang JJ, Wong TY, Smith W, Klein R, Leeder SR (2005) Retinal microvascular signs and risk of stroke and stroke mortality. Neurology 65:1005–1009CrossRefPubMed
48.
Colao A, Sarno AD, Cappabianca P, Briganti F, Pivonello R, Somma CD, Faggiano A, Biondi B, Lombardi G (2003) Gender differences in the prevalence, clinical features and response to cabergoline in hyperprolactinemia. Eur J Endocrinol 148:325–331CrossRefPubMed
Metadata
Title
Microcirculation and atherothrombotic parameters in prolactinoma patients: a pilot study
Authors
Anne Q. Reuwer
Brigitte M. Sondermeijer
Suzanne Battjes
Rogier van Zijderveld
Danka J. F. Stuijver
Peter H. Bisschop
Marcel Th. B. Twickler
Joost C. M. Meijers
Reinier O. Schlingemann
Erik S. Stroes
Publication date
01-12-2012
Publisher
Springer US
Published in
Pituitary / Issue 4/2012
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-011-0353-9

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