Microenvironment and Macroenvironment in Hypertensive Hearts

Abstract

Diastolic heart failure has had a troubled past, with years of uncertainty over its very existence as a specific clinical entity. However, clinicians are seeing growing numbers of patients in our ageing populations where no other adequate and plausible explanation appears to be appropriate. Understandably, a whole literature has grown in attempts to improve sensitivity, specificity, and precision of diagnosis. Heart failure with normal ejection fraction (HFNEF) is the cumbersome term that is now agreed to describe the condition. With progress in availability and capability of echocardiography, HFNEF has attracted the interest of investigators wishing to better understand more basic cellular and molecular mechanisms involved in the development and maintenance of HFNEF, with the aim of developing targeted and effective therapies. Changes in muscle mass, size, and heart shape classically describe cardiac remodeling, but this process is being increasingly linked to dysfunction at the subcellular level, including the extracellular matrix, where alterations in biochemical composition and molecular structure may eventually transition from hypertrophy to heart failure. Activation of different proteases and phospholipases and alterations in gene expression are suggested as the basis for these changes.1 The article by Gonzalez et al2 in this issue of Hypertension makes a bold attempt to unravel some of the complex pathways leading to heart failure with normal ejection fraction, with an emphasis on collagen and the proteolytic tissue digesting matrix metalloproteinases (MMPs) and their antagonists, the tissue inhibitor of metalloproteinases (TIMPs), …