Cellular Senescence In Heart Failure With Preserved Ejection Fraction: Mechanisms And Therapeutic Opportunities
Heart failure with preserved ejection fraction, or HFpEF, is a common and serious heart condition, especially among older adults, where the heart muscle becomes stiff and struggles to fill with blood properly, even though it can still pump blood out effectively. Currently, there are limited effective treatments for this complex syndrome.
Recent research highlights a key player in HFpEF: cellular senescence. Imagine cells in your body that, instead of dying or continuing to divide, simply stop growing and hang around. These are called senescent cells. While this process can sometimes be beneficial, like preventing cancer, an accumulation of these “zombie” cells in tissues, particularly in the heart and blood vessels, can cause problems.
These senescent cells don’t just sit there; they also release a cocktail of inflammatory chemicals, growth factors, and enzymes, collectively known as the Senescence-Associated Secretory Phenotype, or SASP. This SASP creates a harmful environment, promoting inflammation, scarring (fibrosis), and damage to the tiny blood vessels in the heart. These effects are precisely what lead to the stiffness and impaired filling that characterize HFpEF.
The good news is that understanding this connection opens new doors for treatment. Scientists are exploring therapies that either eliminate these senescent cells entirely (called “senolytics”) or block the harmful substances they release (called “senomorphics”). Early studies show promise in reducing the burden of these harmful factors and improving HFpEF. However, challenges remain, such as ensuring these treatments target the right cells and finding reliable ways to monitor their effectiveness in patients.
Source: link to paper