Arya Mani

Bio Profile

Arya Mani, MD, FACC, FAHA

Professor of Medicine (Cardiology) and of Genetics

Director, Cardiovascular Genetics Program

Director, Cardiovascular Module

Research Interests

Cardiology; Genetics; Heart; Heart Defects, Congenital

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Mani Lab

My laboratory’s major focus is the identification of genetic causes of major cardiovascular disorders and the elucidation of their pathophysiology. To achieve this, we have built strong ties at national and international levels with major cardiovascular centers. The goal is to identify and recruit patients and families with diverse cardiovascular disorders that have strong genetic components.


Zibaeenezhad MJ, Ghaem H, Parsa N, Sayadi M, Askarian M, Kasaei M, Sohrabi Z, Dehghani-Firouzabadi A, Nariman A, Radmanesh S, Mani A, Bahramali E, Nikoo MH, Moaref AR, Razeghian-Jahromi I: Analysing cardiovascular risk factors and related outcomes in a middle-aged to older adults population in Iran: a cohort protocol of the Shiraz Heart Study (SHS). BMJ Open. 2019 Apr 3; 2019 Apr 3. PMID: 30948600

Vasconcelos ACCG, Vasconcelos DFP, Pereira da Silva FR, de Carvalho França LF, Alves EHP, Lenardo DD, Dos Santos Pessoa L, Novaes PD, Luiz Dos Reis Barbosa A, Mani A, Mariano FS, Medeiros JR, de Oliveira AP: Periodontitis causes abnormalities in the liver of rats. J Periodontol. 2019 Mar; 2018 Oct 7. PMID: 30216457

Srivastava R, Rolyan H, Xie Y, Li N, Bhat N, Hong L, Esteghamat F, Adeniran A, Geirsson A, Zhang J, Ge G, Nobrega M, Martin KA, Mani A: TCF7L2 (Transcription Factor 7-Like 2) Regulation of GATA6 (GATA-Binding Protein 6)-Dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia. Arterioscler Thromb Vasc Biol. 2019 Feb. PMID: 30567484

Abou Ziki MD, Mani A: The interplay of canonical and noncanonical Wnt signaling in metabolic syndrome. Nutr Res. 2018 Jul 4; 2018 Jul 4. PMID: 30049588

Goetz LG, Mamillapalli R, Sahin C, Majidi-Zolbin M, Ge G, Mani A, Taylor HS: Addition of Estradiol to Cross-Sex Testosterone Therapy Reduces Atherosclerosis Plaque Formation in Female ApoE-/- Mice. Endocrinology. 2018 Feb 1. PMID: 29253190

Mani A: To treat or not to treat: that is the question. J Clin Hypertens (Greenwich). 2018 Jan; 2018 Jan 5. PMID: 29316165

Mani A: Pathogenicity of De Novo Rare Variants: Challenges and Opportunities. Circ Cardiovasc Genet. 2017 Dec. PMID: 29237683

Hwangbo C, Wu J, Papangeli I, Adachi T, Sharma B, Park S, Zhao L, Ju H, Go GW, Cui G, Inayathullah M, Job JK, Rajadas J, Kwei SL, Li MO, Morrison AR, Quertermous T, Mani A, Red-Horse K, Chun HJ: Endothelial APLNR regulates tissue fatty acid uptake and is essential for apelin's glucose-lowering effects. Sci Transl Med. 2017 Sep 13. PMID: 28904225

Mani A: Fragmented QRS: A marker of hypertensive heart disease? J Clin Hypertens (Greenwich). 2017 Sep; 2017 Jul 18. PMID: 28721702

Masoudkabir F, Sarrafzadegan N, Gotay C, Ignaszewski A, Krahn AD, Davis MK, Franco C, Mani A: Cardiovascular disease and cancer: Evidence for shared disease pathways and pharmacologic prevention. Atherosclerosis. 2017 Aug; 2017 Jun 2. PMID: 28624099

Abou Ziki MD, Mani A: Wnt signaling, a novel pathway regulating blood pressure? State of the art review. Atherosclerosis. 2017 Jul; 2017 May 4. PMID: 28522145

Goyal A, Keramati AR, Czarny MJ, Resar JR, Mani A: The Genetics of Aortopathies in Clinical Cardiology. Clin Med Insights Cardiol. 2017; 2017 May 30. PMID: 28607545

Mani A: Local Ancestry Association, Admixture Mapping, and Ongoing Challenges. Circ Cardiovasc Genet. 2017 Apr. PMID: 28408710

Seidelmann SB, Smith E, Subrahmanyan L, Dykas D, Abou Ziki MD, Azari B, Hannah-Shmouni F, Jiang Y, Akar JG, Marieb M, Jacoby D, Bale AE, Lifton RP, Mani A: Application of Whole Exome Sequencing in the Clinical Diagnosis and Management of Inherited Cardiovascular Diseases in Adults. Circ Cardiovasc Genet. 2017 Feb. PMID: 28087566

Vasconcelos DF, Pereira da Silva FR, Pinto ME, Santana LA, Souza IG, Miranda de Souza LK, Oliveira NC, Ventura CA, Novaes PD, Barbosa AL, Medeiros JR, Mikolasevic I, Mani A, Soares de Oliveira J: Decrease of Pericytes is Associated With Liver Disease Caused by Ligature-Induced Periodontitis in Rats. J Periodontol. 2017 Feb; 2016 Sep 26. PMID: 27666673

Li N, Subrahmanyan L, Smith E, Yu X, Zaidi S, Choi M, Mane S, Nelson-Williams C, Behjati M, Kazemi M, Hashemi M, Fathzadeh M, Narayanan A, Tian L, Montazeri F, Mani M, Begleiter ML, Coon BG, Lynch HT, Olson EN, Zhao H, Ruland J, Lifton RP, Mani A: Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus. Am J Hum Genet. 2016 Oct 6. PMID: 27716515

Mani A: White-Coat Hypertension: A True Cardiovascular Risk?: Commentary on "The impact of white-coat hypertension on cardiac mechanics". J Clin Hypertens (Greenwich). 2016 Jul; 2016 Apr 21. PMID: 27098080

Li N, Subrahmanyan L, Smith E, Yu X, Zaidi S, Choi M, Mane S, Nelson-Williams C, Behjati M, Kazemi M, Hashemi M, Fathzadeh M, Narayanan A, Tian L, Montazeri F, Mani M, Begleiter ML, Coon BG, Lynch HT, Olson EN, Zhao H, Ruland J, Lifton RP, Mani A: Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus. Am J Hum Genet. 2016 Jun 2; 2016 May 12. PMID: 27181681

Abou Ziki MD, Mani A: Metabolic syndrome: genetic insights into disease pathogenesis. Curr Opin Lipidol. 2016 Apr. PMID: 26825138

Arscott P, Caleshu C, Kotzer K, Kreykes S, Kruisselbrink T, Orland K, Rigelsky C, Smith E, Spoonamore K, Larsen Haidle J, Marvin M, Ackerman MJ, Hadi A, Mani A, Ommen S, Cherny S: A Case for Inclusion of Genetic Counselors in Cardiac Care. Cardiol Rev. 2016 Mar-Apr. PMID: 26186385

Mani A: Albuminuria in Hypertensive Patients: Where the Choice of Antihypertensive Medications Matters:: Commentary on "Several Conventional Risk Markers Suggesting Presence of Albuminuria Are Weak Among Rural Africans With Hypertension". J Clin Hypertens (Greenwich). 2016 Jan; 2015 Aug 26. PMID: 26306894

Hannah-Shmouni F, Seidelmann SB, Sirrs S, Mani A, Jacoby D: The Genetic Challenges and Opportunities in Advanced Heart Failure. Can J Cardiol. 2015 Nov; 2015 Aug 21. PMID: 26518444

Srivastava R, Zhang J, Go GW, Narayanan A, Nottoli TP, Mani A: Impaired LRP6-TCF7L2 Activity Enhances Smooth Muscle Cell Plasticity and Causes Coronary Artery Disease. Cell Rep. 2015 Oct 27; 2015 Oct 17. PMID: 26489464

Martin KA, Mani MV, Mani A: New targets to treat obesity and the metabolic syndrome. Eur J Pharmacol. 2015 Sep 15; 2015 May 19. PMID: 26001373

Wang S, Song K, Srivastava R, Dong C, Go GW, Li N, Iwakiri Y, Mani A: Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a. FASEB J. 2015 Aug; 2015 Apr 27. PMID: 25917329

Wang S, Song K, Srivastava R, Fathzadeh M, Li N, Mani A: The Protective Effect of Transcription Factor 7-Like 2 Risk Allele rs7903146 against Elevated Fasting Plasma Triglyceride in Type 2 Diabetes: A Meta-Analysis. J Diabetes Res. 2015; 2015 Oct 4. PMID: 26576435

Song K, Wang S, Mani M, Mani A: Wnt signaling, de novo lipogenesis, adipogenesis and ectopic fat. Oncotarget. 2014 Nov 30. PMID: 25526027

Song K, Wang S, Huang B, Luciano A, Srivastava R, Mani A: Plasma cardiotrophin-1 levels are associated with hypertensive heart disease: a meta-analysis. J Clin Hypertens (Greenwich). 2014 Sep; 2014 Jul 23. PMID: 25052897

Keramati AR, Fathzadeh M, Mani A: The metabolic syndrome and DYRK1B. N Engl J Med. 2014 Aug 21. PMID: 25140972

Keramati AR, Fathzadeh M, Go GW, Singh R, Choi M, Faramarzi S, Mane S, Kasaei M, Sarajzadeh-Fard K, Hwa J, Kidd KK, Babaee Bigi MA, Malekzadeh R, Hosseinian A, Babaei M, Lifton RP, Mani A: A form of the metabolic syndrome associated with mutations in DYRK1B. N Engl J Med. 2014 May 15. PMID: 24827035

Go GW, Srivastava R, Hernandez-Ono A, Gang G, Smith SB, Booth CJ, Ginsberg HN, Mani A: The combined hyperlipidemia caused by impaired Wnt-LRP6 signaling is reversed by Wnt3a rescue. Cell Metab. 2014 Feb 4. PMID: 24506864

Singh R, Smith E, Fathzadeh M, Liu W, Go GW, Subrahmanyan L, Faramarzi S, McKenna W, Mani A: Rare nonconservative LRP6 mutations are associated with metabolic syndrome. Hum Mutat. 2013 Sep; 2013 Jun 18. PMID: 23703864

Singh R, De Aguiar RB, Naik S, Mani S, Ostadsharif K, Wencker D, Sotoudeh M, Malekzadeh R, Sherwin RS, Mani A: LRP6 enhances glucose metabolism by promoting TCF7L2-dependent insulin receptor expression and IGF receptor stabilization in humans. Cell Metab. 2013 Feb 5. PMID: 23395167

Liu W, Singh R, Choi CS, Lee HY, Keramati AR, Samuel VT, Lifton RP, Shulman GI, Mani A: Low density lipoprotein (LDL) receptor-related protein 6 (LRP6) regulates body fat and glucose homeostasis by modulating nutrient sensing pathways and mitochondrial energy expenditure. J Biol Chem. 2012 Mar 2; 2012 Jan 9. PMID: 22232553

Go GW, Mani A: Low-density lipoprotein receptor (LDLR) family orchestrates cholesterol homeostasis. Yale J Biol Med. 2012 Mar; 2012 Mar 29. PMID: 22461740

Ye ZJ, Go GW, Singh R, Liu W, Keramati AR, Mani A: LRP6 protein regulates low density lipoprotein (LDL) receptor-mediated LDL uptake. J Biol Chem. 2012 Jan 6; 2011 Nov 28. PMID: 22128165

Keramati AR, Singh R, Lin A, Faramarzi S, Ye ZJ, Mane S, Tellides G, Lifton RP, Mani A: Wild-type LRP6 inhibits, whereas atherosclerosis-linked LRP6R611C increases PDGF-dependent vascular smooth muscle cell proliferation. Proc Natl Acad Sci U S A. 2011 Feb 1; 2011 Jan 18. PMID: 21245321

Keramati AR, Sadeghpour A, Farahani MM, Chandok G, Mani A: The non-syndromic familial thoracic aortic aneurysms and dissections maps to 15q21 locus. BMC Med Genet. 2010 Oct 11; 2010 Oct 11. PMID: 20937124

Liu W, Mani S, Davis NR, Sarrafzadegan N, Kavathas PB, Mani A: Mutation in EGFP domain of LDL receptor-related protein 6 impairs cellular LDL clearance. Circ Res. 2008 Nov 21; 2008 Oct 23. PMID: 18948618

Friedman T, Mani A, Elefteriades JA: Bicuspid aortic valve: clinical approach and scientific review of a common clinical entity. Expert Rev Cardiovasc Ther. 2008 Feb. PMID: 18248277

Mani A, Radhakrishnan J, Wang H, Mani A, Mani MA, Nelson-Williams C, Carew KS, Mane S, Najmabadi H, Wu D, Lifton RP: LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science. 2007 Mar 2. PMID: 17332414

Mani A, Radhakrishnan J, Farhi A, Carew KS, Warnes CA, Nelson-Williams C, Day RW, Pober B, State MW, Lifton RP: Syndromic patent ductus arteriosus: evidence for haploinsufficient TFAP2B mutations and identification of a linked sleep disorder. Proc Natl Acad Sci U S A. 2005 Feb 22; 2005 Jan 31. PMID: 15684060

Mani A, Meraji SM, Houshyar R, Radhakrishnan J, Mani A, Ahangar M, Rezaie TM, Taghavinejad MA, Broumand B, Zhao H, Nelson-Williams C, Lifton RP: Finding genetic contributions to sporadic disease: a recessive locus at 12q24 commonly contributes to patent ductus arteriosus. Proc Natl Acad Sci U S A. 2002 Nov 12; 2002 Oct 30. PMID: 12409608