CV Science

Patrick LACOLLEY MD, PhD Applied basic and biological sciences

Course and current status

Patrick Lacolley is specialized in cardiology and entered Inserm in 1987 and rapidly developed a particular interest for cellular and molecular determinants of arterial stiffness, and mechanotransduction in the field of vascular ageing, hypertension and heart failure. From January 2005 to December 2023, he has been director of the Inserm UMR_S 1116 “Acute and chronic cardiovascular deficiency”, with expertise in molecular and vascular cell biology, experimental animal models and cohorts. He has long-standing experience in the field of cell-matrix interactions and is internationally recognized for its expertise in both basic and clinical aspects of vascular smooth muscle cells and mechanobiology.

Scientific summary

My work focuses on the cellular and molecular determinants of arterial stiffness. Arterial stiffness is considered as a clinical entity related to hypertension and aging. I have contributed to demonstrate the role of central and peripheral hemodynamics. My work has helped to establish that arterial stiffness is an independent risk factor. Classically, it was attributed to changes in matrix proteins, mainly elastin and collagen fibers.

My work ranges from understanding the molecular determinants of the mechanical properties of arterial wall components to the pathophysiology of accelerated aging, such as systolic hypertension in the elderly. They have been developed on the basis of fundamental research and preclinical models, and have been validated in clinical studies on cohorts and populations of interest.

My pioneering contribution focused on the fundamental mechanisms of arterial stiffness, demonstrating that vascular smooth muscle cells (VSMCs) were major components of arterial stiffness. A first paper published in 1998 highlighted the role of integrins and fibronectin in arterial stiffness in models of hypertension (Bezie et al, ATVB 1998). We proposed that increased fibronectin and a₅b₁ and a_vb₃ integrins regulated arterial stiffness and vascular integrity at high pressure levels through enhanced cell-matrix interactions. This original concept is now well recognized in the field.

We then published work on the plasticity of VSMCs and, more specifically, the dynamics of focal adhesions as a key regulator of cell/matrix interactions and arterial stiffness (Galmiche et al, Circ Res 2013; Lacolley et al, Physiol Rev 2017; Regnault et al. Annu Rev Physiol 2024). My work is now focusing on nuclear mechanotransduction and epigenetics at the level of VSMCs in vascular disease (Li et al, Eur Heart J Open 2023).

In aging, structural and molecular changes and increased thrombotic events are 2 risk factors that are most often studied separately. In this context, I'm interested in a possible coupling between them within the wall, which has been recognized as highly original, and is based on the complementary nature of my expertise in the vascular wall and that of my colleague Veronique Regnault (DR. Inserm) in hemostasis. We have published a series of papers demonstrating that these links do indeed exist in accelerated aging and end-stage renal failure, which represents one of the most extreme models in terms of arterial stiffness (Tran et al, Kidney Int 2021).