Inflammation SFRN Collaborative Project
Description: Heart failure with preserved ejection fraction (HFpEF) is a form of heart failure associated with metabolic stress and aging (MESA). It often co-occurs with cognitive impairment (CI) and/or pulmonary hypertension (PH). Effective strategies to combat HFpEF, PH, and cognitive decline are badly needed, but the underlying molecular and cellular mechanisms of these diseases are poorly understood. Emerging evidence from the three Centers within the American Heart Association (AHA) Strategically Focused Research Network (SFRN) on Inflammation in Cardiac and Neurovascular Disease supports the hypothesis that inflammation driven by lysosomal, senescence, and immunometabolic mechanisms plays an important role in HFpEF, CI, and PH pathogenesis. Through this SFRN-Wide Collaborative Project, we seek to define the interplay among these processes while promoting synergistic collaborations and training opportunities across the Network. Specific Aim 1 will uncover mechanistic intersections across relevant lysosomal, senescence, and immunometabolic pathways using gain- and loss-of-function studies in two animal models of HFpEF. Specific Aim 2 will define the interplay among these pathways through proteomic, metabolic and immunological profiling of plasma samples from patients with clinical or preclinical HFpEF with or without PH, and under pharmacological inhibition of SGLT2 metabolic signaling or senescence-related Activin signaling. Specific Aim 3 will enhance network cohesiveness and training opportunities by implementing fellow exchanges and regular cross-SFRN virtual symposia. This work will not only advance our understanding of the molecular, cellular and organ-specific effects of metabolic stress and aging, laying a foundation for new therapeutic strategies, but will also enhance training and synergy across the Inflammation SFRN.
Funder: American Heart Association
Amount: $597,300
Funding type: research
Funder scheme: Strategically Focused Research Network Collaborative
Start date: 2025-07-01
End date: 2028-06-30
Investigators: Anthony Rosenzweig, Anthony Rosenzweig
Institution: The Regents of the University of Michigan
Funded outputs count: 1
Funder award ID: 25ISFRNCP1501445
OpenAlex ID: G255067629