From glycosylation to immunometabolism Fundamental processes that drive cardiovascular diseases

Cardiovascular disease represents a diverse group of disorders of the heart and vasculature, frequently triggered by dyslipidemia. Its development is driven by a complex interplay of lipid accumulation, chronic low-grade inflammation, and thrombosis. In this work, we focus on two central processes underlying atherogenesis: residual lipid risk and residual inflammatory risk.
In the first part, we explore residual lipid risk by investigating protein glycosylation, a fundamental posttranslational modification with emerging relevance in lipid metabolism. Our observations reveal that patients with congenital disorders of glycosylation type I, as well as their family members, display reduced LDL-cholesterol levels. Similarly, individuals carrying mutations in ASGR1 show a markedly lower risk of myocardial infarction. These findings point to glycosylation as a previously underappreciated regulator of lipid metabolism and highlight its potential as a novel therapeutic target.
In the second part, we turn to the role of inflammation in atherogenesis. Recent insights reveal how shifts in cellular metabolism can fuel pro-inflammatory programs. Effector lipids act as key modulators of immune cell function, reshaping metabolic pathways and driving activation states. For example, elevated Lp(a) levels have been linked to metabolic changes in valve cells that sustain inflammation and promote progressive stenosis.
Together, these insights underscore the tight interconnection between lipid metabolism and immune regulation in cardiovascular disease, while pointing to novel therapeutic avenues that target both residual lipid and inflammatory risk.