Primary aldosteronism has been associated with myocardial fibrosis, and is the most common cause of secondary hypertension. We previously showed that aldosterone can induce the secretion of galectin-3. The aim of this study was to investigate the association between myocardial fibrosis and plasma galectin-3 level in patients with primary aldosteronism. We prospectively analyzed 11 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008, and 17 patients with essential hypertension as controls. Levels of plasma galectin-3 were determined in both groups, and both groups underwent echocardiography with cyclic variations of integrated backscatter (CVIBS) to characterize tissue initially and 1 year after surgery in the APA group. Diastolic blood pressure, concentration of plasma aldosterone and aldosterone-renin ratio were significantly higher, and serum potassium level and plasma renin activity significantly lower in the APA group compared to the controls. In addition, left ventricular mass index was significantly higher and CVIBS significantly lower in the APA group (7.3±2.0 vs 9.2±1.7 dB, p=0.015). Furthermore, the concentration of plasma galectin-3 was significantly higher in the APA group (2.1±0.9 vs 1.1±0.6 ng/mL, p=0.005) compared to the controls. CVIBS was correlated to plasma galectin-3 level. In the APA group, CVIBS increased significantly (7.3±2.0 to 9.2±2.4 dB, p=0.032) and plasma galectin-3 decreased (2.1±0.9 to 1.2±0.6, p=0.049) 1 year postadrenalectomy. The patients with APA had increased myocardial fibrosis, and this was associated with a higher plasma galectin-3 level. Both increased myocardial fibrosis and plasma galectin-3 level recovered at least partially after adrenalectomy.
RossiGP. Prevalence and diagnosis of primary aldosteronism. Curr Hypertens Rep2010;12:342–8. doi:10.1007/s11906-010-0134-2
2.
RossiGP, Di BelloV, GanzaroliC, . Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism. Hypertension2002;40:23–7. doi:10.1161/01.HYP.0000023182.68420.EB
3.
KozakovaM, BuralliS, PalomboC, . Myocardial ultrasonic backscatter in hypertension: relation to aldosterone and endothelin. Hypertension2003;41:230–6. doi:10.1161/01.HYP.0000052542.68896.2B
4.
LeeHH, HungCS, WuXM, . Myocardial ultrasound tissue characterization of patients with primary aldosteronism. Ultrasound Med Biol2013;39:54–61. doi:10.1016/j.ultrasmedbio.2012.08.023
5.
LinYH, LinLY, ChenA, . Adrenalectomy improves increased carotid intima-media thickness and arterial stiffness in patients with aldosterone producing adenoma. Atherosclerosis2012;221:154–9. doi:10.1016/j.atherosclerosis.2011.12.003
6.
LinYH, WuXM, LeeHH, . Adrenalectomy reverses myocardial fibrosis in patients with primary aldosteronism. J Hypertens2012;30:1606–13. doi:10.1097/HJH.0b013e3283550f93
7.
LinYH, LeeHH, LiuKL, . Reversal of myocardial fibrosis in patients with unilateral hyperaldosteronism receiving adrenalectomy. Surgery2011;150:526–33. doi:10.1016/j.surg.2011.02.006
8.
Di BelloV, GiorgiD, TaliniE, . Incremental value of ultrasonic tissue characterization (backscatter) in the evaluation of left ventricular myocardial structure and mechanics in essential arterial hypertension. Circulation2003;107:74–80. doi:10.1161/01.CIR.0000041045.26774.1C
9.
GalettaF, BerniniG, FranzoniF, . Cardiac remodeling in patients with primary aldosteronism. J Endocrinol Invest2009;32:739–45. doi:10.1007/BF03346529
10.
WeberKT, GerlingIC, KianiMF, . Aldosteronism in heart failure: a proinflammatory/fibrogenic cardiac phenotype. Search for biomarkers and potential drug targets. Curr Drug Targets2003;4:505–16.
11.
RickardAJ, MorganJ, TeschG, . Deletion of mineralocorticoid receptors from macrophages protects against deoxycorticosterone/salt-induced cardiac fibrosis and increased blood pressure. Hypertension2009;54:537–43. doi:10.1161/HYPERTENSIONAHA.109.131110
12.
LinYH, ChouCH, WuXM, . Aldosterone induced galectin-3 secretion in vitro and in vivo: from cells to humans. PLoS ONE2014;9:e95254. doi:10.1371/journal.pone.0095254
13.
LinYH, WangSM, WuVC, . The association of serum potassium level with left ventricular mass in patients with primary aldosteronism. Eur J Clin Invest2011;41:743–50. doi:10.1111/j.1365-2362.2010.02462.x
14.
WuVC, KuoCC, ChangHW, . Diagnosis of primary aldosteronism: comparison of post-captopril active renin concentration and plasma renin activity. Clin Chim Acta2010;411:657–63. doi:10.1016/j.cca.2010.01.027
15.
KuoCC, WuVC, HuangKH, . Verification and evaluation of aldosteronism demographics in the Taiwan Primary Aldosteronism Investigation Group (TAIPAI Group). J Renin Angiotensin Aldosterone Syst2011; 12: 348–57. doi:10.1177/1470320310391329
16.
WuVC, ChaoCT, KuoCC, . Diagnosis and management of primary aldosteronism. Acta Nephrologica2012;26:111–20.
17.
ChaoCT, WuVC, KuoCC, . Diagnosis and management of primary aldosteronism: an updated review. Ann Med2013;45:375–83. doi:10.3109/07853890.2013.785234
YenRF, WuVC, LiuKL, . TAIPAI Study Group. 131I-6beta-iodomethyl-19-norcholesterol SPECT/CT for primary aldosteronism patients with inconclusive adrenal venous sampling and CT results. J Nucl Med2009;50:1631–7. doi:10.2967/jnumed.109.064873
20.
DevereuxRB, ReichekN. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation1977;55:613–18. doi:10.1161/01.CIR.55.4.613
21.
LinYH, ShiauYC, YenRF, . The relation between myocardial cyclic variation of integrated backscatter and serum concentrations of procollagen propeptides in hypertensive patients. Ultrasound Med Biol2004;30:885–91. doi:10.1016/j.ultrasmedbio.2004.04.007
22.
RundbackJH, SacksD, KentKC, . AHA Councils on Cardiovascular Radiology, High Blood Pressure Research, Kidney in Cardiovascular Disease, Cardio-Thoracic and Vascular Surgery, and Clinical Cardiology, . Guidelines for the reporting of renal artery revascularization in clinical trials. American Heart Association. Circulation2002;106:1572–85.
23.
CatenaC, ColussiG, LapennaR, . Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension2007;50:911–18. doi:10.1161/HYPERTENSIONAHA.107.095448
24.
HoritaY, InenagaT, NakahamaH, . Cause of residual hypertension after adrenalectomy in patients with primary aldosteronism. Am J Kidney Dis2001;37:884–9. doi:10.1016/S0272-6386(05)80002-2
25.
WatanabeI, TaniS, WashioT, . Relationship between the plasma levels of brain natriuretic peptide and left ventricular ejection fraction in asymptomatic patients with previous myocardial infarction. Int Heart J2005;46:1007–14. doi:10.1536/ihj.46.1007
26.
WeberKT, BrillaCG, JanickiJS, . Myocardial fibrosis: role of ventricular systolic pressure, arterial hypertension, and circulating hormones. Basic Res Cardiol1991;86(Suppl 3):25–31.
27.
MatsumuraK, FujiiK, OnikiH, . Role of aldosterone in left ventricular hypertrophy in hypertension. Am J Hypertens2006;19:13–18. doi:10.1016/j.amjhyper.2005.05.013
28.
TanabeA, NaruseM, NaruseK, . Left ventricular hypertrophy is more prominent in patients with primary aldosteronism than in patients with other types of secondary hypertension. Hypertens Res1997;20:85–90. doi:10.1291/hypres.20.85
29.
BettencourtP, FerreiraA, Pardal-OliveiraN, . Clinical significance of brain natriuretic peptide in patients with postmyocardial infarction. Clin Cardiol2000;23:921–7. doi:10.1002/clc.4960231213
30.
BrillaCG, PickR, TanLB, . Remodeling of the rat right and left ventricles in experimental hypertension. Circ Res1990;67:1355–64. doi:10.1161/01.RES.67.6.1355
31.
SunY, RamiresFJ, WeberKT. Fibrosis of atria and great vessels in response to angiotensin II or aldosterone infusion. Cardiovasc Res1997;35:138–47. doi:10.1016/S0008-6363(97)00097-7
32.
LokDJ, Van Der MeerP, de la PortePW, . Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study. Clin Res Cardiol2010;99:323–8. doi:10.1007/s00392-010-0125-y
33.
LinYH, LinLY, WuYW, . The relationship between serum galectin-3 and serum markers of cardiac extracellular matrix turnover in heart failure patients. Clin Chim Acta2009;409:96–9. doi:10.1016/j.cca.2009.09.001
CalvierL, Martinez-MartinezE, MianaM, . The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries. JACC Heart Fail2015;3:59–67. doi:10.1016/j.jchf.2014.08.002
36.
Martinez-MartinezE, CalvierL, Fernandez-CelisA, . Galectin-3 blockade inhibits cardiac inflammation and fibrosis in experimental hyperaldosteronism and hypertension. Hypertension2015;66:767–75. doi:10.1161/HYPERTENSIONAHA.115.05876
37.
HallCS, ScottMJ, LanzaGM, . The extracellular matrix is an important source of ultrasound backscatter from myocardium. J Acoust Soc Am2000;107:612–19. doi:10.1121/1.428327
38.
HollandMR, WilkenshoffUM, Finch-JohnstonAE, . Effects of myocardial fiber orientation in echocardiography: quantitative measurements and computer simulation of the regional dependence of backscattered ultrasound in the parasternal short-axis view. J Am Soc Echocardiogr1998;11:929–37. doi:10.1016/S0894-7317(98)70134-8
39.
MaceiraAM, BarbaJ, VaroN, . Ultrasonic backscatter and serum marker of cardiac fibrosis in hypertensives. Hypertension2002;39:923–8. doi:10.1161/01.HYP.0000014616.48920.8F
