A Clinical Perspective of Anti-Fibrotic Therapies for Cardiovascular Disease

Abstract

Cardiac fibrosis are central to various cardiovascular diseases. Research on the mechanisms and therapeutic targets for cardiac fibrosis has advanced greatly in recent years. However, while many anti-fibrotic treatments have been studied in animal models and seem promising, translation of experimental findings into human patients has been rather limited. Thus, several potential new treatments which have shown to reduce cardiac fibrosis in animal models have either not been tested in humans or proved to be disappointing in clinical trials. A majority of clinical studies are of small size or have not been maintained for long enough periods. In addition, although some conventional therapies, such as renin-angiotensin-aldosterone system (RAAS) inhibitors, have been shown to reduce cardiac fibrosis in humans, cardiac fibrosis persists in patients with heart failure even when treated with these conventional therapies, indicating a need to develop novel and effective anti-fibrotic therapies in cardiovascular disease. In this review article, we summarize anti-fibrotic therapies for cardiovascular disease in humans, discuss the limitations of currently used therapies, along with possible reasons for the failure of so many anti-fibrotic drugs at the clinical level. We will then explore the future directions of anti-fibrotic therapies on cardiovascular disease, and this will include emerging anti-fibrotics that show promise, such as relaxin. A better understanding of the differences between animal models and human pathology, and improved insight into carefully designed trials on appropriate end-points and appropriate dosing need to be considered to identify more effective anti-fibrotics for treating cardiovascular fibrosis in human patients.

The Soft- and Hard-Heartedness of Cardiac Fibroblasts: Mechanotransduction Signaling Pathways in Fibrosis of the Heart

“…Drugs targeting the renin-angiotensin-aldosterone system, endothelin, inflammatory cytokines and TGFβ have shown either modest regression of fibrosis, or adverse effects on the vasculature and liver [257]. A beneficial effect of short-term infusion of the endogenous hormone relaxin in acute heart failure has shown promise [258] and anti-fibrotic effects are clear in animal models of cardiac disease.…”

Double Blockade of Aldosterone Receptors as a Method of Elimination Negative Effects of Non-Steroidal Anti-Inflammatory Drugs in Chronic Heart Failure

“…Таким образом, благодаря включению в схему лечения петлевого диуретика торасемида удалось стабилизировать состояние пациента. Важно отметить необходимость своевременного включения торасемида в схему терапии для предотвращения развития фиброза миокарда, когда обратное развитие уже невозможно [8]. Из используемых в настоящее время для терапии ХСН трех петлевых диуретиков (фуросемид, торасемид и буметанид) только торасемид обладает антифибротическими свойствами.…”

Cardiac Progenitor Cells: The Matrix Has You

“…Although angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers, which are among the elective drugs for heart failure treatment, can indeed act directly on remodeling by reducing the detrimental effects of angiotensin II on cardiac fibroblasts activity , the discovery of novel targeted strategies would undoubtedly improve therapeutic efficacy. Multiple molecules are under clinical investigation, but many trials on antifibrotic drugs have been discouraging . Interestingly, a majority of preclinical studies of cardiac cell therapy have evidenced how one of its main effects is the reduction of tissue fibrosis and remodeling, suggesting that a biological cell‐based therapy may provide per se an effective antifibrotic strategy .…”