Age- and Hypertension-Associated Protein Aggregates in Mouse Heart Have Similar Proteomic Profiles

Hypertension. 2016 May;67(5):1006-13. doi: 10.1161/HYPERTENSIONAHA.115.06849. Epub 2016 Mar 14.


Neurodegenerative diseases are largely defined by protein aggregates in affected tissues. Aggregates contain some shared components as well as proteins thought to be specific for each disease. Aggregation has not previously been reported in the normal, aging heart or the hypertensive heart. Detergent-insoluble protein aggregates were isolated from mouse heart and characterized on 2-dimensional gels. Their levels increased markedly and significantly with aging and after sustained angiotensin II-induced hypertension. Of the aggregate components identified by high-resolution proteomics, half changed in abundance with age (392/787) or with sustained hypertension (459/824), whereas 30% (273/901) changed concordantly in both, each P<0.05. One fifth of these proteins were previously associated with age-progressive neurodegenerative or cardiovascular diseases, or both (eg, ApoE, ApoJ, ApoAIV, clusterin, complement C3, and others involved in stress-response and protein-homeostasis pathways). Because fibrosis is a characteristic of both aged and hypertensive hearts, we posited that aging of fibroblasts may contribute to the aggregates observed in cardiac tissue. Indeed, as cardiac myofibroblasts "senesced" (approached their replicative limit) in vitro, they accrued aggregates with many of the same constituent proteins observed in vivo during natural aging or sustained hypertension. In summary, we have shown for the first time that compact (detergent-insoluble) protein aggregates accumulate during natural aging, chronic hypertension, and in vitro myofibroblast senescence, sharing many common proteins. Thus, aggregates that arise from disparate causes (aging, hypertension, and replicative senescence) may have common underlying mechanisms of accrual.

Keywords: aging (cardiac); cardiovascular diseases; hypertension; neurodegenerative diseases; protein aggregates.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aging / genetics*
  • Aging / physiology
  • Animals
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / physiopathology*
  • Cells, Cultured
  • Humans
  • Hypertension / genetics*
  • Hypertension / physiopathology
  • Mice
  • Myofibroblasts / pathology
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / physiopathology
  • Protein Aggregates / genetics
  • Protein Aggregates / physiology
  • Protein Aggregation, Pathological / genetics*
  • Proteomics / methods*
  • Reference Values
  • Tissue Distribution
  • Young Adult


  • Protein Aggregates