Michael J. Toth, PhD

Education:

Training:

Residency

Fellowship

Specialty:

Certifications:

Academic Appointments:

Biography:

Dr. Toth is a member of our research faculty. He received his Ph.D. in Physiology from the University of Maryland in 1997. His studies focused on the effects of chronic heart failure on the peripheral musculature. Following his Ph.D. work, Dr. Toth arrived at the University of Vermont as a postdoctoral fellow to train in the use of stable isotope tracers to study human protein metabolism. While completing his postdoctoral training, he competed successfully for funding from the NIH and joined the UVM faculty in 1998 as a Research Assistant Professor of Medicine. Dr. Toth’s research program has been continuously supported by grants from the NIH since 1999.

Major Research Interests:

Dr. Toth's research has focused on how the syndrome of heart failure affects the peripheral musculature and how changes in skeletal muscle, in turn, contribute to reduced exercise capacity. His recent studies have shown that heart failure patients experience a unique skeletal muscle myopathy characterized by a selective depletion of the contractile protein myosin heavy chain (MHC). This myopathy is manifest at the whole muscle level as a reduction in contractile strength per unit muscle size and reduced MHC content correlated strongly with exercise intolerance, the hallmark symptom of heart failure. Further studies revealed decreased skeletal muscle MHC mRNA content in heart failure patients, which was paralleled by a reduction in insulin-like growth factor-I expression, a growth factor that is known to stimulate MHC gene expression. These findings suggest that heart failure may impair MHC expression in skeletal muscle through alterations in muscle growth factor expression and/or signaling. The focus of on-going studies is to further characterize this myopathy by measuring skeletal muscle structure and function at the level of the single human muscle fiber. Biomechanical measurements of contractile protein function are used together with classic biochemical and ultrastructural approaches to assess MHC content. Additional studies will examine the expression of growth factors in skeletal muscle to explore the potential mechanisms by which heart failure promotes a reduction in skeletal muscle MHC content. Finally, in collaboration with Dr. Phil Ades and the UVM Cardiac Rehabilitation Center, heart failure patients will undergo a 4 month resistance training program to determine the efficacy of this intervention in countering this myopathy and improving skeletal muscle function. 

Grant title:         Skeletal muscle contractile dysfunction in heart failure.
Sponsor:           NIH R01 HL-077418
PI:                    Michael J. Toth

Grant title:         Exercise and weight loss in obese coronary patients.
Sponsor:           NIH R01 HL-072851
PI:                    Philip A. Ades

Publications:

Representative Publications from a total of 24

Persinger R, Janssen-Heininger Y, Wing SS, Matthews DE, LeWinter MM, Toth MJ. Effect of heart failure on the regulation of skeletal muscle protein synthesis, breakdown and apoptosis. Am J Physiol 284:E1001-E1008, 2003.

Goldstein J, Sites CK, Toth MJ. Progesterone stimulates cardiac protein synthesis via receptor dependent pathway. Fertil Steril 82:430-436, 2004.

Toth MJ, Matthews DE, Ades PA, Tischler MD, Van Buren P, Previs M, LeWinter MM. Skeletal muscle myofibrillar protein metabolism in heart failure: relationship to immune activation and functional capacity. Am J Physiol 288:E685-E692, 2005.

Toth MJ, Palmer B, LeWinter MM. Effect of heart failure on skeletal muscle myofibrillar content, isoform expression and calcium sensitivity. Int J Cardiol 107:211-219, 2006.

Toth MJ, Ades PA, LeWinter MM, Tracy RP, Tchernof A. Skeletal muscle myofibrillar mRNA levels in heart failure: relationship to local and circulating growth factors and cytokines. J Appl Physiol 100:35-41, 2006.

Toth MJ, Matthews DE.  Whole-body protein metabolism in chronic heart failure: Relationship to anabolic and catabolic hormones.  J Parenter Enteral Nutr 30:194-201, 2006.

Cooper BC, Sites CK, Fairhurst PA, Toth MJ.  Evidence against a role for ovarian hormones in the regulation of blood flow.  Fertil Steril 86:440-447, 2006.

Toth MJ, Tchernof A.  Effect of age on skeletal muscle myofibrillar mRNA abundance: Relationship to myosin heavy chain protein synthesis rate.  Exp Gerontol 41:1195-1200, 2006.

Cooper BC, Burger NZ, Toth MJ, Cushman M, Sites CK.  Insulin resistance with hormone replacement therapy: Associations with markers of inflammation and adiposity.  Am J Obstet Gynecol 196:123-127, 2007.

Sites CK, Cooper BC, Toth MJ, Gastaldelli A, Arabshahi A, Barnes S.  Effect of a daily supplement of soy protein on body composition and insulin secretion in postmenopausal women.  Fertil Steril  PMID: 17412329, 2007.