Dupuytren’s Contracture and Heart Disease: Any Connection?

Dupuytren’s contracture is a condition where fingers curl inward due to thickened connective tissue in the palm. While primarily affecting hand function, researchers are exploring whether it shares biological mechanisms with heart disease. Understanding this connection could provide insights into broader fibrotic processes in the body.

Fibrotic Changes in the Hand

Dupuytren’s contracture is marked by progressive thickening and tightening of the palmar fascia, a connective tissue layer beneath the skin. It starts with small, firm nodules in the palm, often near the base of the ring and little fingers. Over time, these nodules form fibrous cords that shorten, pulling the fingers into a flexed position. Unlike other fibrotic conditions that involve inflammation or immune activation, Dupuytren’s is driven by an abnormal proliferation of myofibroblasts—cells responsible for wound contraction and extracellular matrix remodeling. These cells produce excessive collagen, primarily type I and type III, leading to dense, fibrotic tissue that restricts movement.

The condition progresses differently in individuals, with some experiencing minor thickening while others develop severe contractures. Genetic predisposition plays a key role, with studies linking specific gene variants, including those related to Wnt signaling and transforming growth factor-beta (TGF-β) pathways, to fibroblast activity and collagen deposition. Environmental and lifestyle factors, such as chronic mechanical stress, alcohol consumption, and diabetes, also contribute to disease onset and severity.

Histological analysis shows a transition from normal fibroblasts to myofibroblasts that express alpha-smooth muscle actin (α-SMA), a marker of contractile activity. This transformation is a hallmark of fibrotic disorders and drives the progressive tightening of the fascia. Unlike normal wound healing, where myofibroblasts eventually die off, in Dupuytren’s, they persist, continuously producing collagen and reinforcing fibrosis. This persistent activation makes early intervention, such as collagenase injections or surgical fasciectomy, more effective in preventing severe deformity.

Links Between Connective Tissue and Cardiac Health

Connective tissue integrity extends beyond Dupuytren’s contracture, influencing organ function throughout the body, including the heart. The extracellular matrix (ECM), composed primarily of collagen and elastin, provides mechanical support to tissues and regulates cellular behavior. In the cardiovascular system, it maintains the elasticity of blood vessels, flexibility of cardiac valves, and tensile strength of the myocardium. Excessive collagen deposition disrupts ECM composition, leading to myocardial fibrosis and valvular dysfunction—conditions that share mechanistic similarities with Dupuytren’s.

Epidemiological studies suggest a link between Dupuytren’s and an increased prevalence of cardiovascular disease, particularly in individuals with metabolic risk factors. Research published in the Journal of the American College of Cardiology highlights that patients with fibrotic disorders often exhibit elevated TGF-β levels, a key regulator of fibroblast activation and ECM production. This signaling pathway is implicated in both palmar fibrosis and cardiac remodeling, where excessive stimulation leads to myocardial fibrosis. This condition stiffens the ventricular walls and impairs diastolic relaxation, increasing the risk of heart failure with preserved ejection fraction (HFpEF).

Beyond myocardial fibrosis, connective tissue abnormalities contribute to aortic stiffness and valvular disease. Aortic stiffness, a predictor of cardiovascular morbidity, results from an imbalance between collagen deposition and elastin degradation in arterial walls. A study in Circulation Research found that individuals with fibrotic skin disorders exhibited increased arterial stiffness, suggesting a systemic fibrotic phenotype. Similarly, excessive collagen accumulation in heart valves, particularly the aortic and mitral valves, can lead to calcific valvular disease, restricting blood flow and increasing cardiac workload. Given that Dupuytren’s involves localized collagen dysregulation, similar fibrotic mechanisms may contribute to cardiovascular changes.

Collagen Pathways and Organ Involvement

Collagen, the primary structural component of connective tissue, ensures mechanical stability across organ systems. In Dupuytren’s, excessive collagen deposition leads to fibrosis, a process not confined to the hand. Dysregulated collagen metabolism is implicated in systemic conditions, including cardiac fibrosis, pulmonary fibrosis, and hepatic cirrhosis. The balance between collagen synthesis and degradation is regulated by TGF-β and matrix metalloproteinases (MMPs). When disrupted, an overabundance of collagen type I and type III accumulates, altering tissue architecture and function.

In the cardiovascular system, pathological collagen remodeling stiffens the myocardium, affecting diastolic function and increasing heart failure risk. Collagen cross-linking, mediated by lysyl oxidase, further exacerbates tissue rigidity, a mechanism observed in both Dupuytren’s and fibrotic heart disease. Similarly, in the lungs, excessive collagen deposition reduces alveolar flexibility, impairing oxygen exchange in conditions like idiopathic pulmonary fibrosis. The liver experiences similar fibrotic remodeling in cirrhosis, where excess collagen disrupts hepatic architecture, leading to portal hypertension and impaired function. While these conditions affect different tissues, they share a common thread—dysregulated fibroblast activity and collagen deposition, suggesting a broader systemic susceptibility.

Ongoing Research on Shared Mechanisms

Scientists are investigating the molecular and genetic factors linking Dupuytren’s contracture with cardiac fibrosis, focusing on shared pathways driving excessive collagen accumulation. Genomic studies have identified overlapping risk variants associated with fibrotic conditions, particularly within regulatory regions influencing fibroblast activity. Large biobank analyses have revealed correlations between Dupuytren’s and cardiovascular disease, suggesting a genetic predisposition to heightened fibrotic responses. These findings have sparked interest in whether targeting specific molecular pathways could mitigate fibrosis in both the hand and the heart.

TGF-β signaling remains central to ongoing research, given its role in fibroblast activation and extracellular matrix remodeling. Investigators are evaluating antifibrotic agents like pirfenidone and losartan to determine whether they could have therapeutic benefits beyond their current clinical applications. Some preclinical models suggest that dampening TGF-β activity slows fibrotic progression in cardiac tissue and reduces myofibroblast proliferation in Dupuytren’s. While promising, these findings require further validation through controlled clinical trials.